Minimum IC50 Research Articles

Synthesis of Novel Substituted Phenyl‐3‐Hydrazinyl‐Quinoxaline‐2‐Amine Derivatives: Evaluation of Antimicrobial Activity and Its Molecular Docking Studies

New series of quinoxaline derivatives (4a–4h) were synthesized by treating 2‐chloro‐3‐hydrazinyl quinoxalin (3) with various anilines. Compound 3 was obtained from the 2,3‐dichloroquinoxaline 2 which was prepared from 4‐dihydroquinoxaline‐2,3‐dione (1). All synthesized compounds (4a–4h) were characterized by various spectral techniques, that is, IR, 1H‐NMR, mass spectroscopy, and elemental analysis and completion of reaction were confirmed by TLC. In vitro antimicrobial activity of synthesized compounds was evaluated using disc diffusion assay against gram‐positive and gram‐negative microbial strains, and then, the minimum inhibitory concentration and IC50 values of compounds were also determined. The results of antimicrobial study revealed that compounds 4e, 4g, and 4a were active and exhibited better inhibitory activities as compared with standard drug amoxicillin. Docking studies were performed by using Argus lab, and all the compounds exhibited good docking scores between −9.53 and −7.94 kcal/mol against dihydrofolate reductase protein fragment from Staphylococcus aureus (PDB ID‐4XE6). Among all compounds, 4e has shown the maximum docking score and found in agreement to in vitro studies.

Multivalency Increases the Binding Strength of RGD Peptidomimetic-Paclitaxel Conjugates to Integrin αV β3.

This work reports the synthesis of three multimeric RGD peptidomimetic‐paclitaxel conjugates featuring a number of αVβ3 integrin ligands ranging from 2 to 4. These constructs were assembled by conjugation of the integrin αVβ3 ligand cyclo[DKP‐RGD]‐CH2NH2 with paclitaxel via a 2′‐carbamate with a self‐immolative spacer, the lysosomally cleavable Val‐Ala dipeptide linker, a multimeric scaffold, a triazole linkage, and finally a PEG spacer. Two monomeric conjugates were also synthesized as reference compounds. Remarkably, the new multimeric conjugates showed a binding affinity for the purified integrin αVβ3 receptor that increased with the number of integrin ligands (reaching a minimum IC50 value of 1.2 nm for the trimeric), thus demonstrating that multivalency is an effective strategy to strengthen the ligand–target interactions.

Antioxidant and Nephroprotective Potential of Aegle marmelos Leaves Extract

ABSTRACTThe nephroprotective activity of hydro-alcoholic (HAEAM) and ethyl acetate (EAEAM) extracts of Aegle marmelos leaves were evaluated against nephrotoxicity induced by cisplatin (CP), a widely used chemotherapeutic agent in cancer therapy. Wistar rats were treated with CP (6 mg.kg–1; i.p.). Treatment groups received the same dose of CP, along with HAEAM and EAEAM (200 and 400 mg.kg–1) orally for 5 d. Blood urea nitrogen (BUN), serum creatinine, and antioxidant enzymes were estimated in renal tissues. EAEAM exhibited minimum IC50 values 6.13 ± 1.05, 67.34 ± 1.7, 59.7 ± 3.9, and 49.17 ± 2.19 μg.mL–1. EAEAM (400 mg.kg–1) decreased the creatinine levels from 2.29 ± 0.387 to 0.96 ± 0.095 mg.dL–1 and BUN from 92.06 ± 7.949 to 38.18 ± 5.686 mg.dL–1 and restored the activities of renal antioxidant enzymes, decreased the lipid peroxidasde (LPO) levels from 158.70 ± 3.542 to 106.91 ± 5.876 nM.g–1, and increased superoxide dismutase (SOD) levels from 12.59 ± 0.463 to 29.95 ± 5.222 U.g–1, glutathione (GSH) from 0.24 ± 0.029 to 0.57 ± 0.048 μM.g–1, and catalase (CAT) from 1.14 ± 0.067 to 3.27 ± 0.296 U.mg–1).

Efficacy of carbosilane dendrimers with an antiretroviral combination against HIV-1 in the presence of semen-derived enhancer of viral infection

Amyloid fibrils, which are present in semen, were considered to be a cause of topical vaginal gel ineffectiveness in vivo after microbicides failed as HIV-1 prophylaxis. Therefore, it was necessary to determine whether a dendrimer was suitable for further evaluation in an in vitro model of semen-enhanced viral infection (SEVI). We demonstrated that SEVI in TZM.bl cell cultures increased the infectivity of R5-HIV-1NL(AD8), pTHRO.c and pCH058.c isolates, causing higher IC50 values for two polyanionic carbosilane dendrimers, G2-STE16 and G3-S16. However, both dendrimers maintained protection rates of 90% at non-toxic concentrations. When dendrimers were combined with Tenofovir/Maraviroc (TDF/MVC), the anti-HIV-1 effect remained at a minimum IC50 increase between 1- and 7-fold in the presence of amyloid fibrils. In peripheral blood mononuclear cells (PBMC), IC50 values were slightly influenced by the presence of semen. In brief, dendrimers combined with antiretrovirals showed a synergistic effect. This result plays a crucial role in new microbicide formulations, as it overcomes the negative effects of amyloid fibrils.

V. NEGUNDO, L. CAMARA AND B. VARIEGATA PLANTS LEAF EXTRACT EXHIBIT CONSIDERABLE IN VITRO ANTIOXIDANT AND ANTICANCER ACTIVITIES

Objective: The study was planned to investigate antioxidant and anticancer activities with the preliminary phytochemical analysis of methanolic extracts of Vitex negundo (V. negundo), Lantana camara (L. camara) and Bauhania variegata (B. variegata) plants leaf extracts.Methods: Phytochemical evaluation was performed for all the extracts, as per the standard methods. In vitro antioxidant activities were performed by using DPPH (2,2-Diphenyl-1-Picrylhydrazyl), ABTS (2, 2'-Azino-Bis-3-Ethylbenzothiazoline-6-Sulfonic Acid) and FRAP (Ferric reducing antioxidant power assay) method and compared with standard antioxidants. The anticancer activity of plant extract was assessed using MTT colorimetric assay.Results: The study of preliminary phytochemical proved the existence of alkaloids, flavonoids and phenolic types of phytochemicals in high amount. Methanolic extract of L. camara shows minimum IC50 value for DPPH assay (48.75±2.34 µg/ml) and FRAP assay (274.66±3.65 µg/ml). In ABTS assay B. variegata extract exhibit minimum IC50 value (60.48±3.01 µg/ml). Lower the IC50 value of extract, higher the effectiveness of the plant. Methanolic extract of all plants methanolic extracts showed anticancer activity against SH-SY-5Y cells (human neuroblastoma cell) but V. negundo was more effective against SH-SY-5Y cells with IC50 value (209 µg/ml) compared to remaining extracts.Conclusion: The current finding accomplished the in vitro activities, so that plant could be a superior source of antioxidant and anticancer drugs. But further in vivo assessment was needed before adding it into the pharma industry.

Effect of 4-methoxy 1-methyl 2-oxopyridine 3-carbamide on Staphylococcus aureus by inhibiting UDP-MurNAc-pentapeptide, peptidyl deformylase and uridine monophosphate kinase.

The present study aimed to investigate the anti-Staphylococcus aureus and anti-biofilm properties of 4-methoxy-1-methyl-2-oxopyridine-3-carbamide (MMOXC) on S. aureus UDP-MurNAc-pentapeptide (MurF), peptidyl deformylase (PDF) and uridine monophosphate kinase (UMPK). The invitro efficacy of MMOXC was evaluated using quantitative polymerase chain reaction, invitro assays and broth microdilution methods. Further, the minimum inhibitory concentration (MIC), IC50 and zone of inhibition were recorded in addition to the anti-biofilm property. MMOXC inhibited pure recombinant UMPK and PDF enzymes with a Ki of 0·37 and 0·49μmoll-1 . However Ki was altered for MurF with varying substrates. The MurF Ki for UMT, d-Ala-d-Ala and ATP as substrates was 0·3, 0·25 and 1·4μmoll-1 , respectively. Real-time PCR analysis showed a significant reduction in PDF and MurF expression which correlated with the MIC90 at 100μmoll-1 and IC50 in the range 42±1·5 to 50±1μmoll-1 against all strains tested. At 5μmoll-1 MMOXC was able completely to remove preformed biofilms of S. aureus and other drug resistant strains. MMOXC was able to kill S. aureus and drug resistant strains tested by inhibiting MurF, UMPK and PDF enzymes and completely obliterated preformed biofilms. Growth reduction and biofilm removal are prerequisites for controlling S. aureus infections. In this study MMOXC exhibited prominent anti-S. aureus and anti-biofilm properties by blocking cell wall formation, RNA biosynthesis and protein maturation.

Proanthocyanidin Characterization and Bioactivity of Extracts from Different Parts of Uncaria tomentosa L. (Cat's Claw).

Apart from alkaloids, bioactive properties of Uncaria tomentosa L. have been attributed to its phenolic constituents. Although there are some reports concerning low-molecular-weight polyphenols in U. tomentosa, its polymeric phenolic composition has been scarcely studied. In this study, phenolic-rich extracts from leaves, stems, bark and wood (n = 14) of Uncaria tomentosa plants from several regions of Costa Rica were obtained and analysed in respect to their proanthocyanidin profile determined by a quadrupole-time-of-flight analyser (ESI-QTOF MS). Main structural characteristics found for U. tomentosa proanthocyanidins were: (a) monomer composition, including pure procyanidins (only composed of (epi)catechin units) and propelargonidins (only composed of (epi)afzelechin units) as well as mixed proanthocyanidins; and (b) degree of polymerization, from 3 up to 11 units. In addition, U. tomentosa phenolic extracts were found to exhibit reasonable antioxidant capacity (ORAC (Oxygen Radical Absorbance Capacity) values between 1.5 and 18.8 mmol TE/g) and antimicrobial activity against potential respiratory pathogens (minimum IC50 of 133 µg/mL). There were also found to be particularly cytotoxic to gastric adenocarcinoma AGS and colon adenocarcinoma SW620 cell lines. The results state the particularities of U. tomentosa proanthocyanidins and suggest the potential value of these extracts with prospective use as functional ingredients.

Investigation of the Phytochemicals, Antioxidant, and Antimicrobial Activity of the <i>Andrographis paniculata</i> Leaf and Stem Extracts

Andrographis paniculata (Kalmegh) has been considered as a medicinal shrub and used as a medicinal plant in the remote areas of Bangladesh. A. paniculata leaf and stem extracts were prepared using the polar (i.e., water, and 70% ethanol) and nonpolar (i.e., hexane) solvents. The phytochemical contents, total phenol contents (TPC), antioxidant activity, and antibacterial activity of all the extracts of A. paniculata leaf and stem were investigated. Both the gram-positive (i.e., Bacillus subtillis) and gram-negative (i.e., E. coli, and Salmonella typhi) strains of bacteria were used for the antibacterial activity assay of the sample extracts. The ethanolic stem extracts contained the maximum amount of TPC when compared to that of the leaf extracts. However, the aqueous stem extracts had the highest free radical scavenging activity in vitro. The extracts prepared from A. paniculata stem showed better antibacterial activity against all the strains of bacteria (i.e., E. coli, S. typhi, and B. subtillis) when compared to that of the leaf extracts. More specifically, the aqueous stem extract showed superior antibacterial effect against E. coli, and B. subtillis, and the zones of inhibition were 21 mm, and 29 mm in diameter, respectively. On the other hand, the ethanolic stem extract showed the maximum antibacterial activity against S. typhi and the zone of inhibition was 8.15 mm. The minimum inhibitory concentration (MIC) value and IC50 value for all the A. paniculata extracts were ~0.05 μg/μL, and ~1 μg/μL, respectively.

Production of Angiotensin-I-Converting-Enzyme-Inhibitory Peptides in Fermented Milks (Lassi) Fermented by Lactobacillus acidophillus with Consideration of Incubation Period and Simmering Treatment

The lassi, fermented milks product containing angiotensin-I-converting-enzyme (ACE)-inhibitory peptides were produced by using selected Lactobacillus acidophilus NCDC-15 and the incubation period and simmering effect was also optimized for production of ACE-inhibitory peptides. The time–temperature combination for the heat treatment was optimized using RSM. The biological activity was measured in the supernatant of the fermented milk after centrifugation. The lowest IC50 values for the inhibition of angiotensin-converting enzyme (ACE) was found 28.9 ± 0.95 μg protein/ml in the supernatant of milk fermented by L. acidophilus and heated at 78 °C for 10 h. The fractions which showed the highest ACE-inhibitory indexes were further purified by different techniques including solid phase extraction, RP-HPLC and FPLC and the related peptides were identified by LC–MS/MS using the Ultimate 3000 nano HPLC system (Dionex) coupled to a 4000 Q TRAP electro-spray ionization mass spectrometry. The high ACE-inhibitory activity containing fractions of the milk fermented by L. acidophilus contained the sequences of b-casein (b-CN) fragment. The fraction-III showed minimum IC50 value i.e. 14.57 ± 0.72 μg/ml compared with fraction-I and fraction-II. Among these peptides 14 peptides have been identified from the fraction-I of the lassi prepared from L. acidophilus i.e. β-CN f47–56, β-CN f47–57, β-CN f199–209, β-CN f176–182, β-CN f176–183, β-CN f176–184, β-CN f1–7, β-CN f57–68, β-CN f166–175, β-CN f195–206, β-CN f195–207, β-CN f195–209, β-CN f94–106 and β-CN f169–176 showed partially or completely homology to that the milk protein bioactive peptides having ACE inhibitory. The two peptides KVLPVPQK (β-CN f169–176) and YQEPVLGPVRGPFPIIV (β-CN f193–209) have the same sequence as ACE inhibitory peptides (Maeno et al. in J Dairy Sci 79(8):1316–1321, 1996; Yamamoto et al. in J Dairy Sci 77:917–922, 1994b).

CD44 targeted chemotherapy for co-eradication of breast cancer stem cells and cancer cells using polymeric nanoparticles of salinomycin and paclitaxel

This combinational therapy is mainly aimed for complete eradication of tumor by killing both cancer cells and cancer stem cells. Salinomycin (SLM) was targeted towards cancer stem cells whereas paclitaxel (PTX) was used to kill cancer cells. Drug loaded poly (lactic-co-glycolic acid) nanoparticles were prepared by emulsion solvent diffusion method using cationic stabilizer. Size of the nanoparticles (below 150nm) was determined by dynamic light scattering technique and transmission electron microscopy. In vitro release study confirmed the sustained release pattern of SLM and PTX from nanoparticles more than a month. Cytotoxicity studies on MCF-7 cells revealed the toxicity potential of nanoparticles over drug solutions. Hyaluronic acid (HA) was coated onto the surface of SLM nanoparticles for targeting CD44 receptors over expressed on cancer stem cells and they showed the highest cytotoxicity with minimum IC50 on breast cancer cells. Synergistic cytotoxic effect was also observed with combination of nanoparticles. Cell uptake studies were carried out using FITC loaded nanoparticles. These particles showed improved cellular uptake over FITC solution and HA coating further enhanced the effect by 1.5 folds. CD44 binding efficiency of nanoparticles was studied by staining MDA-MB-231 cells with anti CD44 human antibody and CD44+ cells were enumerated using flow cytometry. CD44+ cell count was drastically decreased when treated with HA coated SLM nanoparticles indicating their efficiency towards cancer stem cells. Combination of HA coated SLM nanoparticles and PTX nanoparticles showed the highest cytotoxicity against CD44+ cells. Hence combinational therapy using conventional chemotherapeutic drug and cancer stem cell inhibitor could be a promising approach in overcoming cancer recurrence due to resistant cell population.

Formation and stabilization of the telomeric antiparallel G-quadruplex and inhibition of telomerase by novel benzothioxanthene derivatives with anti-tumor activity.

G-quadruplexes formed in telomeric DNA sequences at human chromosome ends can be a novel target for the development of therapeutics for the treatment of cancer patients. Herein, we examined the ability of six novel benzothioxanthene derivatives S1–S6 to induce the formation of and stabilize an antiparallel G-quadruplex by EMSA, UV-melting and CD techniques and the influence of S1–S6 on A549 and SGC7901 cells through real-time cell analysis, wound healing, trap assay methods. Results show that six compounds could differentially induce 26 nt G-rich oligonucleotides to form the G-quadruplex with high selectivity vs C-rich DNA, mutated DNA and double-stranded DNA, stabilize it with high affinity, promote apoptosis and inhibit mobility and telomerase activity of A549 cells and SGC7901 cells. Especially, S1, S3, S4 displayed stronger abilities, of which S3 was the most optimal with the maximum ΔTm value being up to 29.8 °C for G-quadruplex, the minimum IC50 value being 0.53 μM and the maximum cell inhibitory rate being up to 97.2%. This study suggests that this type of compounds that induce the formation of and stabilize the telomeric antiparallel G-quadruplex, and consequently inhibit telomerase activity, leading to cell apoptosis, can be screened for the discovery of novel antitumor therapeutics.

English

In this study, the ethanolic extract of Justicia adhatoda (Acanthaceae) leaves was prepared by successive extraction procedure in increasing polarity order. Moreover, there are no antimutagenic evaluation reports found. In the present study our aim was to determine the antioxidant and antimutagenic potential of different fractions of ethanolic extract of J. adhatoda. Ultra high performance liquid chromatography (UHPLC) analysis revealed the presence of polyphenolic compounds and flavonoids which might be responsible for bioprotective activity. Among the five fractions (hexane, chloroform, ethyl acetate, n-butanol and aqueous), n-butanol and ethyl acetate exhibited significant antioxidant activity with minimum IC50 value (< 105.33 µg/ml) whereas, hexane, chloroform and aqueous fractions exhibits excellent antimutagenic potential against 2-aminofluorine for S. typhimurium TA98 and TA100 strains in the presence of S9 mix. These results indicate that these fractions need further research into its potential chemoprevention effects.   Key words: Justicia adhatoda, antioxidant, antimutagenic, ultra-high performance liquid chromatography (UHPLC), IC50 value.

Anionic Self Micro-Emulsifying Drug Delivery System(SMEDDS) Of Docetaxel for Circulation Longevity

Anionic Self Micro-Emulsifying Drug Delivery System(SMEDDS) Of Docetaxel for Circulation Longevity In the present study, we present anionic self microemulsifying drug delivery system (SMEDDS) of DTX for long circulation comprising of ethyl oleate, Tween-80, propylene glycol and dimethyl acetamide. The anionic charge was induced by including two different anionic surface active agents Sodium oleate and Gantrez AN-119 which localized at the oil water interface as evident by the negative zeta potential of -16mV and -26mV respectively. Hemolysis <15% exhibited by SMEDDS confirmed safety for intravenous administration. Intravenous administration of formulations at dose equivalent to 2.5 mg/kg DTX revealed comparable pharmacokinetics of SMEDDS and Gantrez SMEDDS with the marketed formulation. The Sodium oleate containing SMEDDS however revealed a 2 fold increase in half life and significantly lower Vd and clearance confirming circulation longevity as compared to other formulations. In vitro cytotoxicity in A549 cell line (human alveolar cell line) revealed maximum cytotoxicity with minimum IC50 shown by SMEDDS containing sodium oleate. Furthermore, significant increase in DTX uptake due to sodium oleate SMEDDS in A-549 cell line suggested superiority of the sodium oleate SMEDDS, both in circulation longevity and possible enhanced efficacy.

In vitro anticancer and antioxidant activity studies on Drosera peltata J.E.Sm.

Aim: The present study aimed to assess the in vitro antioxidant and anticancer properties of Drosera peltata J.E.Sm. Methods: Antioxidant capacity of the extracts were tested on hydroxyl, DPPH, super oxide, nitric oxide and ABTS radicals; of ferrous ion chelating ability and by reducing power assay. Ascorbic acid was used as the standard antioxidant for the above all assay methods. Dalton’s Ascitic Lymphoma (DAL) and Ehrlich Ascitic Carcinoma (EAC) were used as cell lines to assess its in vitro anticancer effect. Tryphan blue dye and LDH leakage assays were carried out to know its anticancer potential. Moreover, total flavonoid content was estimated to find out the exact reason for its antioxidant potential. Results: The aqueous extract (AEDP) in comparison with the ethanol extract (EEDP), showed considerable antioxidant and anticancer activities in all the models tested. The minimum IC50 values of 48.87 ± 0.53 mcg/ml was shown by EEDP in metal chelating assay and 28.46 ± 0.7 mcg/ml by AEDP in hydroxyl radical scavenging assay. Higher doses of both extracts (250mcg/ml) showed significant cytotoxic effects on DAL and EAC of LDH leakage assay model. Total flavonoid contents of both extracts were estimated and expressed as mg/g quercetin equivalent (QE), where ethanol extract was rich in flavonoid content than aqueous extract. Conclusion: These study results were concluded that D. peltata exhibited excellent antioxidant activity against free radicals which were generated from different models and showed very good anticancer activity against the two cell lines, this results might be due to the phytoconstituent such as flavonoid present in the plant extracts.

Characterization of Salmonella Typhimurium DNA gyrase as a target of quinolones.

Quinolones exhibit good antibacterial activity against Salmonella spp. isolates and are often the choice of treatment for life-threatening salmonellosis due to multi-drug resistant strains. To assess the properties of quinolones, we performed an in vitro assay to study the antibacterial activities of quinolones against recombinant DNA gyrase. We expressed the S. Typhimurium DNA gyrase A (GyrA) and B (GyrB) subunits in Escherichia coli. GyrA and GyrB were obtained at high purity (>95%) by nickel-nitrilotriacetic acid agarose resin column chromatography as His-tagged 97-kDa and 89-kDa proteins, respectively. Both subunits were shown to reconstitute an ATP-dependent DNA supercoiling activity. Drug concentrations that suppressed DNA supercoiling by 50% (IC50 s) or generated DNA cleavage by 25% (CC25 s) demonstrated that quinolones highly active against S. Typhimurium DNA gyrase share a fluorine atom at C-6. The relationships between the minimum inhibitory concentrations (MICs), IC50 s and CC25 s were assessed by estimating a linear regression between two components. MICs measured against S. Typhimurium NBRC 13245 correlated better with IC50 s (R = 0.9988) than CC25 s (R = 0.9685). These findings suggest that the DNA supercoiling inhibition assay may be a useful screening test to identify quinolones with promising activity against S. Typhimurium. The quinolone structure-activity relationship demonstrated here shows that C-8, the C-7 ring, the C-6 fluorine, and N-1 cyclopropyl substituents are desirable structural features in targeting S. Typhimurium gyrase.

Effects of dog rose and watercress extracts on control of green mould decay and postharvest quality of orange fruits

Minimum inhibitory concentration (MIC) and IC50 values and total phenolics of dog rose fruits were 72.5–80 μL mL− 1, 130 μg mL− 1 and 5.7 mg GA g− 1, respectively. The Fashand watercress population and dog rose extracts exhibited mycelia growth inhibition values of 45.08% and 37.12%, respectively. The results of in vivo study indicated that the treatment of inoculated fruits with both methanol extracts especially the watercress plant extract considerably controls the citrus fruits decay (Penicillium digitatum) up to 73%. In conclusion, methanol extracts of dog rose fruits and especially watercress plant had the potential to be used against citrus green mould and even for the improvement of postharvest quality of orange fruits.

Estimation of total phenolics and flavonoidal contents as well as in vitro antioxidant potential of Apium leptophyllum Pers.

Abstract At present, major causes of diseases is oxidative stress affecting both metabolic and physiological functions of the body. That is why there is a great need for investigation of nutritious food supplements for counteracting these oxidative stresses. Therefore, the aim of study was to evaluate the therapeutic potential of Apium leptophyllum Pers. fruits by estimating total phenolic as well as flavonoidal contents and antioxidant values. The collected fruits were extracted separately using different solvents like methanol, ethanol and water. Total phenolic and flavonoid contents were measured from the respective extracts and correlated with their antioxidant values. The antioxidant properties of various fruit extracts (12.5, 25, 50, 100 and 150 μg/ml) were evaluated by DPPH, hydroxyl, nitric oxide and superoxide scavenging assay and compared with ascorbic acid as a standard. All the extracts of A. leptophyllum were found to be dose dependent inhibition against these free radicals. Among all these extracts, the methanolic one was found better in the scavenging activity and followed dose-dependent manner against DPPH, hydroxyl radical, nitric oxide, superoxide anions with minimum IC50 values of 97.9, 89.02, 135.37, 127.73 μg/ml, respectively, and also observed more significant (p&lt;0.01) as compared with standard Furthermore, total phenolic and flavonoidal contents were found highest in methanolic extract. The results obtained in this study clearly indicate that the methanolic extract of A. leptophyllum may be used as a new potential source of natural nutritional supplement in food or pharmaceutical industries due to rich source of phenolic, flavonoidal contents as well as antioxidant property

Microwave-assisted synthesis and antibacterial activity of derivatives of 3-[1-(4-fluorobenzyl)-1H-indol-3-yl]-5-(4-fluorobenzylthio)-4H-1,2,4-triazol-4-amine

AbstractHerein, an excellent method for the synthesis of twelve novel Schiff base derivatives containing indole and triazole assisted by microwave irradiation is reported. Compared with the conventional method, the yields increased from 59–84 % to 85–96 % and the reaction time was reduced from 24–30 h to 4–8 min. Moreover, all series of the newly synthesized Schiff bases were evaluated for their antibacterial activity. The values of minimum inhibitory concentration (MIC) and IC50 indicated that many target compounds possessed excellent antibacterial activity against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Bacillus subtilis.

Anticancer and antimicrobial evaluation of newly synthesized steroidal 5,6 fused benzothiazines

A series of new 5α-cholestano [5,6-b] benzothiazines (4–6) has been synthesized by the reaction of 5α-cholestan-6-one (1–3) with 2-aminothiophenol in the presence of iodine. The structures of newly synthesized compounds have been established on the basis of spectral and analytical data. Compounds (1–6) were screened for in vitro anticancer activity against the human cancer cell lines; SW480 (colon adenocarcinoma cells), A549 (lung carcinoma cells), HepG2 (hepatic carcinoma cells) and HeLa (cervical cancer cells) using MTT assay during which the products (4–6) showed marked increase in anticancer activity and in particular, compound 6 showed IC50=13.73μmolL−1 against HeLa cells, being more effective than Doxorubicin against the same cells. Compounds 4 and 6 also showed minimum IC50 of 15.83μmolL−1 and 16.89μmolL−1 against HepG2 and A549 cells, respectively. Compounds (1–6) were also tested for in vitro antimicrobial activity against different bacterial as well as fungal strains during which newly synthesized compounds (4–6) were found more potent than starting compounds (1–3). Compound 4 was found to be more potent than the reference drug, Chloramphenicol, in the case of Escherichia coli while compound 5 was found almost equally potential antifungal agent against P. marneffei in comparison with the reference drug, Nystatin.

CeCl3·7H2O-SiO2: Catalyst promoted microwave assisted neat synthesis, antifungal and antioxidant activities of α-diaminophosphonates

CeCl3·7H2O supported on silica (CeCl3·7H2O-SiO2) is used as a heterogeneous, efficient and recyclable catalyst for a three component one-pot reaction of an amine, aldehydes and diethyl phosphite to synthesize α-diaminophosphonate derivatives under microwave irradiation exploiting neat reaction conditions. Ten α-diaminophosphonates (6a–j) of 4,4′-sulfonyldianiline (Dapsone) (3) were synthesized and structural elucidation was confirmed by spectral data. Antifungal and antioxidant activities were evaluated include minimum inhibitory concentrations and IC50 values, respectively of the titled compounds. Compounds 6h, 6i exhibited promising antioxidant activity at lower IC50 values 53.7 μg/mL, 53.2 μg/mL, respectively as compared with standard IC50 value 51.6 μg/mL.