Percentage Of Growth Inhibition Research Articles

Comparative Evaluation of the Anti-cancer Activities of the Crude Extracts of Four Nigerian Chewing Sticks

Chewing sticks are commonly used as oral hygiene tool in Nigeria to prevent different types of oral disease including periodontal disease and dental caries. A link has recently been established between periodontal disease and various types of cancers, including lung and breast cancer. The crude extracts of four Nigerian chewing sticks (Fagara zanthoxyloides, Butyrospermum paradoxum, Distemonanthus benthamianus and Nauclea latifolia) were investigated for anticancer activities against four cancer cell lines (Lung A549, Prostate PC-3, Lung NCI-H322, Breast T47D) using Sulforhodamine B (SRB) assay. The result of this study showed that the extracts inhibited the growth of the cells with F. zanthoxyloides having the highest broad spectrum activity against the four cell lines with growth inhibition of 72 %, 71 %, 79 % and 79 % against Lung A549, Prostate PC-3, Lung NCI-H322 and Breast T47D respectively followed by Nauclea latifolia which had a percentage growth inhibition of 70 %, 62 % and 54 % against Lung NCI-H322, Lung A549 and Breast T47D cells lines while showing a weak inhibition of 23 % against Prostate PC-3 cell lines. Butyrospermum paradoxum had the least activity with growth inhibition of 46 %, 56 %, 45 % and 39 % against Lung A549, Prostate PC-3, Lung NCI-H322 and Breast T47D cells lines respectively. D. benthamianus showed selective activity with growth inhibition of 62 %, 34 %, 30 % and 52 % against Lung A549, Prostate PC-3, Lung NCI-H322 and Breast T47D cell lines respectively. The result therefore justifies the use of these plants in traditional medicine and also demonstrates that F. zanthoxyloides could be a good source of anti-cancer drugs.

Design, synthesis and evaluation of novel sulfonamides as potential anticancer agents

Based on modern literature data about biological activity of E7010 derivatives, a series of new sulfonamides as potential anticancer drugs were rationally designed by QSAR modeling methods Сlassification learning QSAR models to predict the tubulin polymerization inhibition activity of novel sulfonamides as potential anticancer agents were created using the Online Chemical Modeling Environment (OCHEM) and are freely available online on OCHEM server at https://ochem.eu/article/107790. A series of sulfonamides with predicted activity were synthesized and tested against 60 human cancer cell lines with growth inhibition percent values. The highest antiproliferative activity against leukemia (cell lines K-562 and MOLT-4), non-small cell lung cancer (cell line NCI-H522), colon cancer (cell lines NT29 and SW-620), melanoma (cell lines MALME-3M and UACC-257), ovarian cancer (cell lines IGROV1 and OVCAR-3), renal cancer (cell lines ACHN and UO-31), breast cancer (cell line T-47D) was found for compounds 4–9. According to the docking results the compounds 4–9 induce cytotoxicity by the disruption of the microtubule dynamics by inhibiting tubulin polymerization via effective binding into colchicine domain, similar the E7010.

BIOLOGICAL ACTIVITY AND DISINFECTION OF ANOSAN SOLUTION WITH INHERENT APPLICABILITY 1- INACTIVATION OF PATHOGENIC MICROORGANISMS

The pathogenic and spoilage microorganisms affect human health directly or indirectly and become increasingly important in most countries. Novel antimicrobial agents and disinfectants have become necessary due to the rise of antibiotic resistance phenomena. The current study investigate the inhibitory infect of ANOSAN on pathogenic bacteria and toxigenic fungi. Chemical analysis was performed for ANOSAN. The antimicrobial activity of ANOSAN was carried out using agar well diffusion assay and mean growth inhibition percentage and Minimum Inhibitory Concentration (MIC). The antibiofilm activity was conducted using Biofilm formation assay and the impact of the disinfectant on the preformed biofilm was visualized by Scanning Electron Microscope (SEM). The chemical composition of ANOSAN comprised very low amount of Sodium (0.034%), Chloride (0.01%), Hypochlorite (0.014%) and Organic matter (0.0062%). ANOSAN low concentration showed a broad spectrum of antibacterial activities against Gram positive, Gram negative bacteria and fungi. The MIC (0.781 mg/ml) was observed for Vibrio cholerae, Pseudomonas aeruginosa and Staphylococcus aureus. Sub-inhibitory concentrations of ANOSAN have successfully inhibited biofilm formation of the above mentioned bacterial patho gens. The ANOSAN appeared to be effective as bactericidal against Ps. aeruginosa and Staph. aureus. The time kill assay was observed between (0-6h) and between (0-3h) of exposure for both pathogens, respectively, and the viable bacterial counts remained undetectable after the previous time in a confirmatory experiment. Scanning Electron Microscopy (SEM) was conducted to confirm the antimicrobial activity of ANOSAN against Staph. aureus and Ps. aeruginosa. These data directly illustrate the destructive effects of the ANOSAN on the pathogenic bacteria. This work clarified that ANOSAN water had bactericidal and fungicidal activity along with inhibiting the ability of pathogenic bacteria to form biofilms, thus providing a good alternative to the use of traditional antimicrobials in food industry, pharmaceutical and medical applications.

Synthesis, characterization and antibacterial activity of novel heterocycle, coumacine, and two of its derivatives

Heterocyclic nucleus plays a fundamental role in the medicinal chemistry and serves as a key template for the development of various therapeutic agents including broad spectrum antibacterial drugs. In an effort to develop new antibacterial agents, a bicyclic twelve-membered heterocyclic nucleus derived from coumarin was prepared by an uncomplicated method. The rate of ring closure for this nucleus, which was given the name coumacine, in addition to two of its derivatives was monitored spectroscopically and this rate followed zero order kinetics. The chemical structures of the synthesized products were established by detecting their physicochemical properties and analyzing their IR, 1H NMR and 13C NMR spectra. The in vitro antibacterial activity of coumacines was evaluated via agar dilution method against different standard aerobic and anaerobic bacterial strains using ciprofloxacin and metronidazole as positive controls, respectively; the results indicated that coumacine I has an excellent broad spectrum antibacterial activity against the tested bacterial strains with percentage of growth inhibition approximating to those of positive controls.

Correlation between live attenuated measles viral load and growth inhibition percentage in non-small cell lung cancer cell line

Correlation between live attenuated measles viral load and growth inhibition percentage in non-small cell lung cancer cell line

Rationale Design, Synthesis, Cytotoxicity Evaluation, and Molecular Docking Studies of 1,3,4-oxadiazole Analogues.

1,3,4-Oxadiazole heterocycles possess a broad spectrum of biological activities. They were reported as potent cytotoxic agents and tubulin inhibitors; hence it is of great interest to explore new oxadiazoles as cytotoxic agents targeting tubulin polymerization. Two new series of oxadiazoles (5a-h and 12a-h) were synthesized, structurally related to the heterocyclic linked aryl core of IMC-038525, NSC 776715, and NSC 776716, with further modification by incorporating methylene linker. The 2,5-disubstituted-1,3,4-oxadiazoles (5a-h and 12a-h) were synthesized by refluxing an equimolar mixture of the intermediates [(4) and (8a-d)] and aromatic aldehydes in water-ethanol system using sodium bisulphite catalyst. The cytotoxicity evaluation was carried out according to the National Cancer Institute (NCI US) Protocol, while the tubulin polymerization assay kits from Cytoskeleton ™(bk011p) was used to perform an in vitro tubulin polymerization assay. 2-(5-{[(4-Chlorophenyl)amino]methyl}-1,3,4-oxadiazol-2-yl)phenol (5f) and 2-[(2,4-dichlorophenoxy) methyl]-5-(3,4-dimethoxyphenyl)-1,3,4-oxadiazole (12c) showed maximum cytotoxicity with the mean percent growth inhibitions (GIs) of 71.56 and 72.68 respectively at 10 µM drug concentrations. Both the compounds (5f and 12c) showed superior cytotoxicity than clinically prevalent anticancer drugs, Imatinib and Gefitinib in one dose assay. The compound 12c showed promising results in five dose assay, with GI50 values varies between 1.61 and >100 µM. Furthermore, the compounds, 5f and 12c also inhibited the polymerization of tubulin with, an IC50 of 2.8 and 2.2 µM, respectively. The oxadiazoles reported herein are tubulin inhibitors and cytotoxic agents. These findings will be helpful in future drug design of more potent tubulin inhibitor cytotoxic agents.

Population diversity of bacterial endophytes from jute (Corchorus olitorius) and evaluation of their potential role as bioinoculants

Endophytes are bacterial or fungal organisms associated with plants in an obligate or facultative manner. In order to maintain a stable symbiosis, many of the endophytes produce compounds that promote plant growth and help them adapt better to the environment. This study was conducted to explore the potential of jute bacterial endophytes for their growth promotion ability in direct and indirect ways. A total of 27 different bacterial species were identified from different varieties of a jute plant (Corchorus olitorius) and different parts of the plant (leaf, root, seed, and seedling) based on 16S rRNA gene sequence. Two of the isolates showed ACC deaminase activity with Staphylococcus pasteuri strain MBL_B3 and Ralstonia solanacearum strain MBL_B6 producing 18.1 and 8.08 μM mg−1 h−1 α-ketobutyrate respectively while eighteen had the ACC deaminase gene (acdS). Fourteen were positive for siderophore activity while Kocuria sp. strain MBL_B19 (133.36 μg/ml) and Bacillus sp. strain MBL_B17 (124.72 μg/ml) showed high IAA production ability. Seven bacterial strains were able to fix nitrogen with only one testing positive for nifH gene. Five isolates exhibited phosphorus utilization ability with Bacillus sp. strain MBL_B17 producing 218.47 μg P/ml. Three bacteria were able to inhibit the growth of a phytopathogen, Macrophomina phaseolina and among them Bacillus subtilis strain MBL_B4 was found to be the most effective, having 82% and 53% of relative inhibition ratio (RIR) and percent growth inhibition (PGI) values respectively. Nine bacteria were tested for their in vivo growth promotion ability and most of these isolates increased seed germination potential and vigour index significantly. Bacillus subtilis strain MBL_B13 showed 26.8% more vigour index than the control in which no bacterial inoculum was used. All inoculants were found to increase the dry weight of jute seedlings in comparison to the control plants and the most increase in fresh weight was found for Staphylococcus saprophyticus strain MBL_B9. Staphylococcus pasteuri strain MBL_B3 exhibited diverse in vitro growth promotion activity and significant growth promoting effect in in vivo pot experiments. These bacterial strains with plant growth enhancing abilities have the potential to be used as bioinoculants.

Strains of soil microorganisms promising for the creation of a complex plant protection product against mycoses and harmful insects

We evaluated the antagonistic activity of 23 strains of Bacillus spр. against phytopathogenic fungi Fusarium oxysporum, F. culmorum, F. moniliforme, Cladosporium herbarum, Alternaria alternata and Aspergillus niger. The antagonistic activity was tested by agar diffusion (the method of blocks). For determining the influence of bacteria on barley plants , ardent seeds were treated by cultural liquid (dilution 1 : 10) for 2 hours and germinated in Petri dishes on moist filter paper. The fungistatic effect of Bacillus sрp. separately and in combination with entomopathogens (in equal ratio) was determined by the level of inhibition of the fungi Fusarium spp. on a solid nutrient medium with 5% of the culture liquid. Insecticidal activity of microorganisms was determined in the model experiments by the percentage of death of the caterpillar Archips podana Scop. Strains of Bacillus sp. KMB-3 and Bacillus sp. KMB-6 inhibited the growth of all test cultures (zones of growth inhibition 11.4–30.6 and 11.5–29.4 mm, respectively). We established the absence of antagonism between selected strains and entomopathogenic bacteria Bacillus thuringiensis IMB-7186, fungi Beauveria bassiana IMB-F-100043. We found that treatment of barley seeds with culture liquids of Bacillus sp. KMB-3 and Bacillus sp. KMB-6 didn’t have a negative effect on the morphometric indices and dry weight of seedlings. We established that the highest percentage of growth inhibition of F. culmorum IMB-F-50716 was provided by a complex of Bacillus sp. KMB-3, B. bassiana IMB-F-100043 and B. thuringiensis IMB-7186, whose action was at the same level as the action of monoculture Bacillus sp. KMB-3 (85.4% and 84.7%, respectively). The highest percentage inhibition of growth of F. oxysporum ІМВ-F-54201 was provided by a complex of strains of Bacillus sp. KMB-3 and B. bassiana IMB-F-100043, whose effect was slightly inferior to that of the monoculture Bacillus sp. KMB-3 (68.4% and 75.1%, respectively). The insecticidal activity of complexes Bacillus sp. KMB-3, B. bassiana IMB-F-100043, B. thuringiensis IMB-7186 or Bacillus sp. KMB-6, B. bassiana IMB-F-100043, B. thuringiensis IMB-7186 insignificantly differed from that of the complex entomopathogens B. bassiana IMB-F-100043 and B. thuringiensis IMB-7186 (71.1%, 73.3% death versus 80.0%). The selected microbial complexes can be considered as promising for the development of a preparation for the protection of plants against fungal diseases and harmful insects.

Enhanced Antitumor Effects of Epidermal Growth Factor Receptor Targetable Cetuximab-Conjugated Polymeric Micelles for Photodynamic Therapy.

Nanocarrier-based delivery systems are promising strategies for enhanced therapeutic efficacy and safety of toxic drugs. Photodynamic therapy (PDT)—a light-triggered chemical reaction that generates localized tissue damage for disease treatments—usually has side effects, and thus patients receiving photosensitizers should be kept away from direct light to avoid skin phototoxicity. In this study, a clinically therapeutic antibody cetuximab (C225) was conjugated to the surface of methoxy poly(ethylene glycol)-b-poly(lactide) (mPEG-b-PLA) micelles via thiol-maleimide coupling to allow tumor-targetable chlorin e6 (Ce6) delivery. Our results demonstrate that more C225-conjugated Ce6-loaded polymeric micelles (C225-Ce6/PM) were selectively taken up than Ce6/PM or IgG conjugated Ce6/PM by epidermal growth factor receptor (EGFR)-overexpressing A431 cells observed by confocal laser scanning microscopy (CLSM), thereby decreasing the IC50 value of Ce6-mediated PDT from 0.42 to 0.173 μM. No significant differences were observed in cellular uptake study or IC50 value between C225-Ce6/PM and Ce6/PM groups in lower EGFR expression HT-29 cells. For antitumor study, the tumor volumes in the C225-Ce6/PM-PDT group (percentage of tumor growth inhibition, TGI% = 84.8) were significantly smaller than those in the Ce6-PDT (TGI% = 38.4) and Ce6/PM-PDT groups (TGI% = 53.3) (p < 0.05) at day 21 through reduced cell proliferation in A431 xenografted mice. These results indicated that active EGFR targeting of photosensitizer-loaded micelles provides a possible way to resolve the dose-limiting toxicity of conventional photosensitizers and represents a potential delivery system for PDT in a clinical setting.

Predicting tumour growth and its impact on survival in gemcitabine-treated patients with advanced pancreatic cancer

The aim of this evaluation was to characterize the impact of the tumour size (TS) effects driven by the anticancer drug gemcitabine on overall survival (OS) in patients with advanced pancreatic cancer by building and validating a predictive semi-mechanistic joint TS-OS model.TS and OS data were obtained from one phase II and one phase III study where gemcitabine was administered (1000-1250 mg/kg over 30-60 min i.v infusion) as single agent to patients (n = 285) with advanced pancreatic cancer. Drug exposure, TS and OS were linked using the population approach with NONMEM 7.3.Pancreatic tumour progression was characterized by exponential growth (doubling time = 67 weeks), and tumour response to treatment was described as a function of the weekly area under the gemcitabine triphosphate concentration vs time curve (AUC), including treatment-related resistance development. The typical predicted percentage of tumour growth inhibition with respect to no treatment was 22.3% at the end of 6 chemotherapy cycles. Emerging resistance elicited a 57% decrease in drug effects during the 6th chemotherapy cycle. Predicted TS profile was identified as main prognostic factor of OS, with tumours responders' profiles improving median OS by 30 weeks compared to stable-disease TS profiles. Results of NCT00574275 trial were predicted using this modelling framework, thereby validating the approach as a prediction tool in clinical development.Our analyses show that despite the advanced stage of the disease in this patient population, the modelling framework herein can be used to predict the likelihood of treatment success using early clinical data.

Antioxidant and Cytotoxicity Potential of Six Synthesized Chalcones

Background: Chalcones are open-chain flavonoids which display a large number of pharmacological activities such as cytotoxic, anti-inflammatory including antioxidant. The objective of this study was to assess antioxidant and cytotoxic activity of six synthesized chalcones. Methodology: For the current experiments, 1,3-diphenylpropenone (compound R) was used as molecular model to synthetize six compounds, namely three benzyl-benzimidazolyl-chalcones (U1, U2, WAC1) and three imidazopyridinyl-chalcones (V1, V2, V3). All the compounds were evaluated for their ability to scavenge the stable free ABTS.+ radical cation, according to the method develop by Choong et al. In addition, the cytotoxicity test described by Price et al., was performed using healthy human cell line, then in human malignant cell lines (HEP-2, A549). Results: All synthesized chalcones reduced the ABTS.+ radical cation. Indeed, benzyl benzimidazolyl compounds WAC1, U1, U2, by developing respectively 39.61%, 66.09%, and 84.20% percentages of reduction, showed an antioxidant effect 6, 11 and 14 times greater than the compound R (6.14%). As a result, imidazopyridinyl-chalcones compounds, namely V1, V2 and V3 reduced the ABTS.+ radical cation at 91.62%, 99.84% and 97.45% respectively, being 15 and 16 times more active than the compound R. About cytotoxicity, V2 inhibited not significantly HEP-2 malignant cells growth at 48.64%, compared to the standard product, i.e. doxorubicin that inhibited the growth of the same cells at 42.37%. WAC1 inhibited significantly the growth of A549 malignant cells at 89.53%, more than doxorubicin which percentage of growth inhibition was 71.58%. Conclusion: The presence of the α, β-unsaturated carbonyl system (or 1,3-diphenylpropenone) along with a benzimidazole or imidazopyridine heterocyclic ring is likely to contribute to both cytotoxic and antioxidant activities of these compounds.

Effects of plant extracts on controlling wheat blast disease caused by Magnaporthe oryzae Pathotype triticum in Bangladesh

The present research work was conducted to evaluate the efficacy of twelve plant extracts viz. Neem (Azadirachta indica), Bishkatali(Polygonum hydropiper), Nishinda (Vitex negundu), Allamonda (Allamanda cathertica), Acasia (Acacia auriculiformis), Tulsi (Ocientific tenuiflorum), Mehendi (Lmetawsonia alba), Datura (Datura metel), Bishkochu (Alocasia fornicate), Black cumin (Nigella sativa), Garlic (Allium sativum), Mehogoni (Swietenia macrophylla) @ 1:10 along with two fungicides Provax and Nativo @ 0.2% as check against Magnaporthe oryzae Pathotype triticum which is responsible for wheat blast disease at Department of Plant Pathology, Bangladesh Agricultural University and Plant Pathology Division, Bangladesh Institute of Nuclear Agriculture (BINA), Mymensingh-2202. This experiment was conducted in two phases viz. laboratory and pot experiment. In the laboratory experiment, the efficacies of plant extracts were evaluated by the measurement of percent inhibition of radial mycelial growth of M. oryzae Pathptype triticum. The highest percentage of mycelial inhibition (93.75%) was recorded in case of four plant extracts namely Tulsi, Mehendi, Datura and Garlic followed by Black cumin seed extracts (90%) at 10 days after inoculation, where as Allamonda leaf extract showed lowest percentage of mycelial growth inhibition (7.5%). On the basis of in vitro test five plant extracts were selected to conduct pot experiment to evaluate the disease incidence and severity, and some yield contributing parameters in treated and control plants. Minimum percentage of disease incidence and severity were recorded in case of Garlic clove extract ( 16.28 and 3.5) treated plants and the Mehendi leaf extract treated plants showed highest % of disease incidence and severity (66.0% and 68.0%). Garlic clove extracts also showed best performance for yield contributing parameters namely ear length (9.20 cm), number of ear/pot (13.25), number of healthy ear/pot (13.0), number of total and healthy spikelets/ear (34.20 and 33.40),number of total and healthy grains/ear (23.00 and 21.80) and weight of 1000 total and healthy grains/pot (56 and 52 gm) followed by Black cumin, whereas Mehendi leaf extract treated plants showed lowest value for all the yield contributing parameters among the plant extracts used in this experiment. Both in in vito and pot experiment Garlic extract showed best performance and it might be used for the eco-friendly management of blast disease and increase the yield of wheat.

Rubus sanctus Schreb. root extract alters the MicroRNA expression and inhibits tumor activities of colorectal cancer cell lines

Background: Colorectal cancer (CRC) is one of the most common cancers in the world. Although surgical and screening techniques have vastly improved in the last 30 years, chemotherapeutics have not advanced sufficiently for successful treatment. Objective: The aim of this study is to investigate the microRNA (miRNA) expression changes and anticancer agent potential of Rubus Sanctus Schreb. root extract (RRE) on LoVo and HT-29 colorectal adenocarcinoma cell lines. Materials and Methods: LoVo and HT-29 CRC cell lines treated with different concentrations of RRE to find growth inhibitory effect with WST-1 assay. Fifty percent growth inhibition and 25% growth inhibition concentrations further evaluated with annexin V, total caspase, cell cycle, and migration assays. Real-time polymerase chain reaction was used to investigate the expression differences in miRNA after extract treatment. Results: Cell proliferation was reduced 77.98% in HT-29 cells after RRE treatment ( P P P P P Conclusion: Our data show for the first time that RRE has the capability to inhibit CRC cell proliferation and invasion and alter epigenetic mechanisms. Although further studies should be conducted on this topic, RRE is thought to be a potential candidate for the future studies regarding new therapy options. Abbreviation used: RRE: Rubus Sanctus Schreb. root extract; CRC: Colorectal cancer; GI 50 , GI 25: 50% and 25% growth inhibition; miRNA: MicroRNA; MGMT: O-6-Methylguanine-DNA methyltransferase; UTR: Untranslated region; Akt: Protein kinase B; PI3K: Phosphoinositide 3-kinase; NF-κB: Nuclear factor kappaB; iNOS: Inducible nitric oxide synthase; COX-2: cyclooxygenase 2; TNFα: tumor necrosis factor alpha; IL-6: Interleukin 6; DMEM: Dulbecco's Modified Eagle's medium; RPMI-1640: Roswell Park Memorial Institute 1640 medium; HPLC: High-performance liquid chromatography; UV-Vis: Ultraviolet-visible; FBS: Fetal bovine serum; OD: Optical density; RFU: Relative fluorescence unit; PE: Phycoerythrin; 7-AAD: 7-Aminoactinomycin D; PBS: Phosphate-buffered saline; EGFR: Epidermal growth factor receptor; 5-FU: Fluorouracil; MSI: Microsatellite instability; NSCLC: Nonsmall cell lung cancer; TGF-β: Transforming growth factor beta; EMT: Epithelial–mesenchymal transition

Antagonistic potential of Bacillus spp. isolates against bacterial pathogens of tomato and fungal pathogen of pepper

In vitro antagonistic potential of eleven isolates of Bacillus spp. against two phytopathogenic bacteria and one fungus was tested in order to identify potential biocontrol agents in vegetable crops. The Bacillus spp. isolates demonstrated different levels of antagonistic effect against the tested pathogenic microorganisms. Data in the study proved Xanthomonas vesicatoria to be more sensitive to Bacillus spp. strains than Clavibacter michiganensis subsp. michiganensis. Ten B. subtilis strains induced growth inhibition of X. vesicatoria, while a strain of B. pumilus did not affect the growth of that bacterium. The largest inhibition zones against X. vesicatoria were induced by strains B-319, B-325 and B-358. The pathogenic strain C. michiganensis subsp. michiganensis was most inhibited by two B. subtilis strains (B-338 and B-348) with mean inhibition zone diameters of up to 20 mm. B. subtilis strain B-319 which was the best in inhibiting X. vesicatoria, showed the lowest inhibitory effect on C. michiganensis subsp. michiganensis. The largest growth inhibition percentage of Verticillium sp. (PGI approximately 70%) was induced by B. subtilis strains B-310 and B-322. The other B. subtilis strains showed PGI values ranging from 45% to 68%, while B. pumilus strain B-335 had the least antagonistic potential (PGI =34.43%) against the pathogen. This study identified at least one suitable biocontrol candidate, B. subtilis strain B-358, as effective in vitro against all three vegetable pathogens.

Synthesis, Cytotoxic Evaluation, and Molecular Docking Studies of New Oxadiazole Analogues

Background: Cancer is one of the major health diseases worldwide with an approximately 14 million new cases of cancer and 8.2 million cancer related death tolls were reported in 2012. The major complications associated with chemotherapy are limited efficacy, selectivity, safety as well as higher cost, emergence of drug resistant cancer, and genotoxicity. Today we need more effective and safer cytotoxic agents to combat cancer. Method: Two new series of N-(2,6-dimethylphenyl)-5-aryl-1,3,4-oxadiazol-2-amine (4a–g) and N-{[5- aryl-1,3,4-oxadiazol-2-yl]methyl}-2,6-dimethylaniline (4h-n) were designed and synthesized based on the structure of IMC-038525 (tubulin polymerization inhibitor) and NSC 777948 as cytotoxic agents. The cytotoxicity of eight compounds was carried out as per National Cancer Institute (NCI US) protocol on nearly 60 cancer cell lines, while the cytotoxicity of five compounds was carried out as per Sulforhodamine B assay on two breast cancer cell lines. The molecular docking studies implying tubulin inhibition were also carried out to observe the binding mode of new oxadiazoles. Results: N-(2,6-Dimethylphenyl)-5-(4-chlorophenyl)-1,3,4-oxadiazol-2-amine (4b) showed significant cytotoxicity with comparatively higher sensitivity towards colon cancer (HT29), melanoma (LOX IMVI), leukemia (RPMI-8226), and melanoma (M14), with percent growth inhibitions (% GIs) of 80.99, 75.05, 63.25, and 62.19 respectively. Compound 4b showed better cytotoxicity than the standard drug imatinib. Further compound 4b showed maximum docking score and was found to have different binding mode than the rest of the compounds at the colchicine binding site of tubulin enzyme with a hydrogen bonding between NH with carbonyl oxygen of Thr353 (bond length = 3.05A). The hydrophilicity of compound 4b was another parameter that might play a major role and made it most effective when compared to the rest of the compounds. Conclusion: The oxadiazoles reported herein are cytotoxic agents. These findings may be helpful in future drug design of more potent cytotoxic agents. Keywords: Anticancer agent, cytotoxic agents, oxadiazoles, one dose assay, molecular docking, sulforhodamine B assay.

The Potential Use of Plant Growth-Promoting Rhizobacteria (PGPR) as Antagonists and Biocontrol Agents in Hevea Diseases

The rhizosphere related bacterial species have a significant capability in plant growth promotion, referred to as Plant Growth Promoting Rhizobacteria (PGPR). Several substances produced by antagonistic rhizobacteria have been related to pathogen control and indirect promotion of growth in many plants. The objectives of this study were to identify effective PGPR bacteria in rubber soils of Sri Lanka, determine the potential use as antagonists and biocontrol agents to control economically important Hevea diseases in nurseries, and identify effective novel inoculant formulations. Soil samples were collected from the root rhizozphere of cover crops in Hevea fields in Rubber Research Institute of Sri Lanka (RRISL), Dartonfield. Bacteria were isolated by TSA plate method. Isolated PGPR bacteria were subjected to test the enzyme secretion ability. Pectinase, Lipase, and Amylase secretion ability of PGPR were tested in specifically developed media. Auxin production of PGPR were measured using freshly prepared Salkowsky reagent. Phosphorous solubilizing ability of PGPR was tested using Pikovskaya (PVK) medium. Antagonistic ability of PGPR was tested against the Rigidoporous microporus, Fusarrium sp. and Pythium sp. causing white root disease and Patch Canker disease in rubber respectively. Paper disc diffusion method was used to test the antagonism of selected bacteria and the percentage growth inhibition was calculated. Plasmid DNA extraction of antagonistic PGPR was done following the alkaline SDS method. Gene sequencing of selected bacteria was further carried out. Among 13 selected PGPR bacterial species, 3 bacteria were showing significant antagonism towards R. microporus. (Percentage growth inhibition by 51.2%, 46.8% and 44.3% respectively) Fusarium sp. was controlled by 7 PGPR species. Pythium sp. was controlled by 2 PGPR (Percentage growth inhibition by 41.6% and 38.7% respectively) 5 types of combinations of bacteria were tested. Among 5 types, 2 types were highly effective in control of R. microporus (Percentage growth inhibition by 79.8% and 72.6% respectively). All 5 combinations were moderately effective in control Fusarium sp. and 1 type was highly effective in control of Pythium sp. (Percentage growth inhibition by 67.8%). PGPR can be used as effective biocontrol agents in control of Hevea pathogens. The combinations of PGPR are more effective than the individual bacterial species. This will be leading to improve the productivity of Hevea plantations in Sri Lanka. Keywords: Plant Growth Promoting Rhizobacteria, Antagonism, Hevea pathogens

Synthesis and biological potentials of some new 1,3,4-oxadiazole analogues

In continuation of our research to explore new antiproliferative agents, we report herein the synthesis and antiproliferative activity of two new series of N-(substituted phenyl)-5-aryl-1,3,4-oxadiazol-2-amine (4a–j) and N-{[5-aryl-1,3,4-oxadiazol-2-yl]methyl}-substituted aniline (4k–t) analogs. The antiproliferative activity of fifteen compounds (4a–h, and 4n) was tested against nine different panels of nearly 60 NCI human cancer cell lines. N-(2-Methoxyphenyl)-5-(4-chlorophenyl)-1,3,4-oxadiazol-2-amine (4b) and 4-{5-[(2-Methoxyphenyl)amino]-1,3,4-oxadiazol-2-yl}phenol (4c) showed maximum antiproliferative activity among the series with a mean growth percents (GPs) of 45.20 and 56.73, respectively. The compound 4b showed significant percent growth inhibitions (GIs) on nearly 47 cancer cell lines and were found to have higher sensitivity towards HL-60(TB), MDA-MB-435, OVCAR-3, and K-562 with percent GIs (GIs) of 109.62, 105.90, 91.94, and 88.30, respectively. Similarly the compound, 4c showed significant percent GIs on nearly 42 cancer cell lines and were found to have higher sensitivity towards UO-31, MDA-MB-435, KM12, and K-562 with %GIs of 84.31, 80.52, 78.65, and 77.06, respectively. Both the compounds 4b and 4c showed better antiproliferative activity than the standard drug Imatinib while the antiproliferative activity of compound 4b was found to be nearly comparable to the standard drug 5-flurouracil (5-FU). The antiproliferative activity of five compounds (4o-s) was tested against the breast cancer cell lines (MCF-7 and MDA-MB-231) as per Sulforhodamine B assay (SRB assay). N-{[5-(4-Methoxyphenyl)-1,3,4-oxadiazol-2-yl]methyl}-4-methylaniline (4p) was found to have significant antiproliferative activity against MCF-7 and MDA-MB-231 with GI50 of 12.9 and 59.3 µM, respectively. Further, the free radical scavenging activity results were significant for the most active compounds, 4b (IC50 = 21.07 µM) and 4c (IC50 = 15.58 µM). The docking studies was also carried against tubulin enzyme and the most active compound (4b) showed good interaction with the residues Lys254, Ala250, Cys241, Val318, Ala316, Asn258, and Lys352 present in the hydrophobic cavity of tubulin.

Synthesis and Biological Activity of Novel (Z)- and (E)-Verbenone Oxime Esters.

Twenty-seven (Z)- and (E)-verbenone derivatives bearing an oxime ester moiety were designed and synthesized in search of novel bioactive molecules. Their structures were confirmed by UV-Vis, FTIR, NMR, ESI-MS, and elemental analysis. The antifungal and herbicidal activities of the target compounds were preliminarily evaluated. As a result, compound (E)-4n (R = β-pyridyl) exhibited excellent antifungal activity with growth inhibition percentages of 92.2%, 80.0% and 76.3% against Alternaria solani, Physalospora piricola, and Cercospora arachidicola at 50 µg/mL, showing comparable or better antifungal activity than the commercial fungicide chlorothalonil with growth inhibition of 96.1%, 75.0% and 73.3%, respectively, and 1.7−5.5-fold more growth inhibition than its stereoisomer (Z)-4n (R = β-pyridyl) with inhibition rates of 22.6%, 28.6% and 43.7%, respectively. In addition, seven compounds displayed significant growth inhibition activity of over 90% against the root of rape (Brassica campestris) at 100 µg/mL, exhibiting much better herbicidal activity than the commercial herbicide flumioxazin with a 63.0% growth inhibition. Among these seven compounds, compound (E)-4n (R = β-pyridyl) inhibited growth by 92.1%, which was 1.7-fold more than its stereoisomer (Z)-4n (R = β-pyridyl) which inhibited growth by 54.0%.

Design, Synthesis, Antitumor activity, cell cycle analysis and ELISA assay for Cyclin Dependant Kinase-2 of a new (4-aryl-6-flouro-4H-benzo[4, 5] thieno[3, 2-b] pyran) derivatives.

A series of benzo[b]thiophene and their benzo[4,5]thieno[3,2-b]pyran derivatives (3a-f), (4a-f), (5a-f) and 6 were synthesized and characterized by spectroscopic and elemental analysis. All compounds were subjected to one dose anticancer screening in NCI- America, but only the compounds gave high percent growth inhibition were further subjected to five dose screening. A good result of compound 4f with GI50 = 0.15 µmol, TGI= 1.14 µmol and 4c with GI50 = 1.09 µmol, TGI = 10.19 µmol, LC50 = 100 µmol on HT-29 cell line. To explore mechanism of cytotoxicity, compound 4f and 4c were allowed to affect cell cycle progression using HT-29 cell line (human colon cancer) in two-time interval (24 and 48 hr). The cytotoxicity of 4f and 4c was correlated with induction of apoptosis causing pre-G1apoptosis and cell growth arrest at G2/M in a time dependant manner through inhibition of CDK-2. For exploring the SAR for all synthesized compounds, IC50 of 5d was determined which was equal to 0.32 ±0.05 µmol, IC50 of 6 was equal to be 0.15 ±0.01 µmol while IC50 of erlotinib reference was equal to 0.3±0.02 µmol. Finally we were able to synthesize a series of benzo[b] thiophene, benzo[4,5]thieno[3,2-b]pyran having a good cytotoxic activity suggesting promising anticancer derivatives.

Evaluation of growth inhibition activity of myxobacterial extracts against multi-drug resistant Acinetobacter baumannii

The worldwide dissemination of multi drug resistant Acinetobacter baumannii strains has caused serious concern and high rate of mortality in recent decades that originate from limited effective antibiotics in the treatment of A. baumannii infections. Myxobacteria are Gram-negative bacteria that are important for their complex lifestyle and production of novel structurally secondary metabolites with diverse bioactivities. In this study, a total of 60 myxobacterial strains were purified by culturing and investigation of 130 soil samples. Secondary metabolite extracts of the selected strains were screened for antibacterial activity against multi-drug resistant (MDR) Acinetobacter baumannii. The most potent extracts derived from Stigmatella sp. UTMC 4081, Stigmatella sp. UTMC 4072, and Archangium sp. UTMC 4070 which were investigated by recording percentage of growth inhibition, MIC, MBC, and IC50 values. The results showed that the MIC value of extract No. 4072 was 2.5 μg/ml and its MBC value against A. baumannii recorded as 5 μg/ml. Extract No. 4081 was known to be active with MIC of 2.5 μg/ml and MBC of 10 μg/ml. In addition, MIC and MBC values of extract No. 4070 were found to be 10 and 25 μg/ml, respectively. Myxobacterial extracts showed no toxicity against Artemia salina. This study demonstrated the importance of myxobacterial metabolites as promising antimicrobial agents against multi drug resistant A. baumannii Keywords: Myxobacteria; Stigmatella; Antimicrobial activity; Multi-drug resistant bacteria