Standard Drug Doxorubicin Research Articles

Exploring the Potential of Substituted 4-Thiazolidinone Derivatives in the Treatment of Breast Cancer: Synthesis, Biological Screening and In Silico Studies

A series of 4-thiazolidinone conjugates bearing quinoline/indole/furan scaffolds were designed as potential anti-breast cancer agents, synthesized, and investigated for their anti-breast cancer, and anti-oxidant activity. The anticancer activity was performed using MTT assay against breast cancer cell lines such as MCF-7 and MDA-MB-231 and the results demonstrated that most of the compounds were sensitive to cancer cell lines. Compounds GT1, GT2 and GT5 showed remarkable potency against MCF-7 cell lines with IC50 values of 11.64 µM, 11.27 µM and 11.37 µM respectively in comparison to standard drug doxorubicin with IC50 value of 11.80 µM. Compounds GT2 and GT5 exerted higher cytotoxic activity against the MDA-MD-231 cell line with IC50 value of 17.60 µM and 15.09 µM respectively than doxorubicin (IC50: 18.35 µM). The anti-oxidant activity was also performed by DPPH and hydrogen peroxide scavenging assay. Compounds GT2 and GT7 showed higher free radical scavenging activity with IC50 value of 11.39 µM and 11.28 µM respectively against DPPH assay and 10.99 µM and 11.20 µM respectively against hydrogen peroxide assay. The molecular docking study was carried out against estrogen receptor alpha (PDB ID: 4IVY) to identify the mechanism of action of synthesized compounds using molecular docking and molecular dynamics simulation. The results showed that compounds GT1, GT2, and GT5 showed higher docking score −110.922 kcal/mol, −124.618 kcal/mol and-116.029 kcal/mol respectively as compared to reference (doxorubicin) drug (-109.847 kcal/mol). The ADME and toxicity profile was predicated by Schrodinger QikProp program. All the synthesized compounds showed no violation of Lipinski’s rule except GT2. The molecule insight behavior was predicted by using MD simulation. According to in silico and in vitro studies GT1, GT2, and GT5 showed anti-cancerous activity against MCF-7.

Diaporine Potentiates the Anticancer Effects of Oxaliplatin and Doxorubicin on Liver Cancer Cells.

Recent studies have shown that diaporine, a novel fungal metabolic product, has a strong in vitro and in vivo anticancer effect on human non-small-cell lung and breast cancers. In this study, three human hepatocarcinoma cell lines (HepG2, Hep3B, and Huh7) were used to evaluate the efficacy of diaporine alone and in combination with the standard cytotoxic drugs oxaliplatin and doxorubicin for the treatment of liver cancer. We demonstrated that diaporine, oxaliplatin, and doxorubicin triggered a concentration- and time-dependent decrease in the number of HepG2 cells. Diaporine at a concentration of 2.5 μM showed almost 100% inhibition of cell counts at 72 h. Similar effects were observed only with much higher concentrations (100 μM) of oxaliplatin or doxorubicin. Decreases in cell numbers after 48 h treatment with diaporine, oxaliplatin, and doxorubicin were also demonstrated in two additional hepatoma cell lines, Hep3B and Huh7. The combination of these drugs at low concentration for 48 h in vitro noticeably showed that diaporine improved the inhibitory effect on the number of cancer cells induced by oxaliplatin or doxorubicin. Additionally, this combination effectively inhibited colony growth in vitro. We found that inhibition of phosphorylation of ERK1/2 significantly increased when diaporine was used in combination with other agents. In addition, we also found that when diaporine was used in combination with doxorubicin or oxaliplatin, their proapoptotic effect greatly increased. We further revealed that the induction of apoptosis in hepatoma cells after treatment is due, at least in part, to the inhibition of phosphorylation of AKT, leading to the activation of caspase-3, inactivation of poly (ADP-ribose) polymerase (PARP), and subsequently to DNA damage, as indicated by the increased level of H2AX. Based on these findings, we suggest that diaporine in combination with the standard cytotoxic drugs oxaliplatin and doxorubicin may play a role in the treatment of liver cancer.

Synthesis and in vitro anticancer evaluation of 8b-hydroxy-1-(6-substitutedbenzo[d]thiazol-2-yl)-3-(3-substitutedphenyl)-1,8b-dihydroindeno[1,2-c]pyrazol-4(3aH)-ones

A series of 1,8b-dihydroindeno[1,2-c]pyrazol-4(3aH)-ones has been efficiently synthesized on reaction of 2-(3-substitutedbenzoyl)-(1H)-indene-1,3(2H)-diones 1 and 2-hydrazinylbenzo[d]thiazole/2-hydrazinyl-6-substitutedbenzo[d]thiazoles 2 in presence of dry ethanol under reflux conditions in good yields. The structures of all the synthesized derivatives were elucidated by using different physical and spectral techniques (FTIR, 1H NMR, 13C NMR, 2D NMR and HRMS). The synthesized hydroxypyrazolones were assayed for their anticancer activity against two human cancer cell lines (i) lung carcinoma (A549) and (ii) breast carcinoma (MCF7) using MTT assay. Among all the tested compounds, 3d and 3k with IC50 values in the range of 30.68 ± 0.57 µM to 34.87 ± 0.76 µM exhibited moderate inhibitory ability against both the tested cancer cell lines in comparison to the standard drug Doxorubicin (0.95 ± 0.10 µM for A549 and 1.09 ± 0.11 µM for MCF7). The moderately active compounds of the series i.e.3d and 3k were further tested against normal human embryonic kidney cell line (HEK 293T) to examine their toxicity against normal cell lines. Selectivity Index (S.I.) of the most active compounds 3d and 3k was calculated for both the cancer cell lines which revealed that these derivatives i.e. 3d (S.I = 2.82 for A549 and 2.90 for MCF7) and 3k (S.I = 2.78 for A549 and 2.95 for MCF7) are safer anticancer agents.

Synthesis, biological evaluation,and in silico studies of indole-tethered pyrazoline derivatives as anticancer agents targeting topoisomerase IIα.

We herein report a new series of indole-tethered pyrazoline derivatives as potent anticancer agents. A total of12compounds were designed and synthesized by conventional as well as microwave-irradiated synthesis methods. The latter method results in a significant reduction in the duration of reaction along with improved yields. All synthesized derivatives (7a-7l) were evaluated for their cytotoxic activity against A431, HeLa, and MDAMB-231 cell lines. Compounds 7a and 7b were found most potent in the series and demonstrated an IC50 value of 3.17 and 5.16 µM against the A431 cell line, respectively, compared to the standard drug doxorubicin. Compounds 7a and 7b significantly suppress colony formation, migration, and S phase cell cycle arrest of A431 cells. Furthermore, compound 7a regulated the expression of apoptotic proteins causing the downregulation of procaspase 3/9, antiapoptotic protein Bcl-xL, and upregulation of proapoptotic protein Bax in a dose-dependent manner. Topoisomerase enzyme inhibition assay confirmed that compounds 7a and 7b can significantly inhibit topoisomerase IIα. In vivo oral acute toxicity of compounds 7a and 7b revealed that both compounds are safe compared to doxorubicin; cardiomyopathy studies showed normal architecture of cardiomyocytes and myofibrils. In addition, molecular docking studies revealed the possible interaction of compounds 7a and 7b within the active binding site of the topoisomerase enzyme. The 100 ns molecular dynamicsimulation of compounds 7a and 7b proved that both compounds validate all screening parameters.

Rational synthesis, anticancer activity, and molecular docking studies of novel benzofuran liked thiazole hybrids.

A novel series of benzofuran bearing thiazole hybrids were synthesized by the multistep reaction approach. All synthesized molecules were selected by the National Cancer Institute, USA for one-dose anticancer activity against 60 various human cancer cell lines indicating nine types of cancer. Among thirteen compounds, two compounds showed higher lethality, so, it was selected for five-dose anticancer screening against all cancer cell lines. Compound 8g and 8h were displayed remarkable antiproliferative activity with GI50 values ranging from 0.295 to 4.15μM and LC50 values ranging from 4.43 to > 100μM. All data are compared with standard drugs fluorouracil and doxorubicin. Compound 8g showed higher potency as a cytotoxic molecule then fluorouracil. Furthermore, all new hybrids were studied for molecular docking into the active binding sites of 1HOV protein.

Design, synthesis and cytotoxic activity studies of alkyne linked analogues of Nimbolide

A series of novel nimbolide derivatives bearing various substitutions on 28th position was designed and synthesized using Sonogashira (2a-2p) and Glaser coupling (3a-3e) reactions. The synthesized derivatives were assessed for in vitro cytotoxic activity against four different human cancer cell lines (A549 cells, MCF-7 cells, MDA-MB-231 cells, and HCT15 cells) and normal cell line (HEK cells) using MTT assay. Among the screened derivatives, the compound 3a showed potent activity against A549 cells with IC50 value of 0.23 μM as comparing with parent molecule 1 (1.48 μM) and the standard drug doxorubicin (0.82 μM). As well, the flow cytometry analysis confirmed that the compounds 1 and 3a arrest the cell cycle progress at S phase and induce the early apoptosis in the lung cancer. The qRT-PCR analysis revealed that the compounds 1 and 3a downregulate the BcL2 expression and upregulates the Bax gene expression level in A549 cells. The strong binding affinity of the compounds 1 and 3a with BcL2 was also confirmed using molecular docking analysis. Together, the results suggested that the compound 3a is a promising anticancer agent against lung cancer is deserved for further investigation.

Lamotrigine derivatives‐synthesis, anti‐cancer, and anti‐MDR‐bacterial activities

A new series of quaternary ammonium salts 3–21 of lamotrigine (6-(2, 3-dichlorophenyl)-1, 2, 4-triazine-3, 5-diamine) was synthesized via N-alkylation of lamotrigine using different benzyl bromides. The new analogues were characterized by using FT-IR, NMR, and mass spectrometric techniques. Single-crystal X-ray diffraction analysis of compound 10 was also carried out to confirm the position of substitution and salt formation. All the compounds 3-21 were tested for various biological activities, including anti-bacterial, and anti-cancer properties. All compounds, except 20, exhibited a potent growth inhibition of Staphylococcus aureus strains as compared to the ofloxacin, the standard drug. Compounds 4, 7, 10, and 13 showed a significant toxicity towards HeLa cell line (derived from cervical carcinoma), whereas compounds 3, and 5 showed a significant activity towards HeLa, MCF-7 (estrogen and progesterone positive breast cancer cell line), and MDA-MB cell lines (epithelial, human breast cancer cell line), as compared to the standard drug doxorubicin. To the best of our knowledge all analogues of 6-(2, 3-dichlorophenyl)-1, 2, 4-triazine-3, 5-diamine, and their activity against MDR, and anti-cancer is reported here for the first time.

Ramachary-Bressy-Wang [3+2]cycloaddition reaction: Synthesis of fully decorated 1,2,3-triazoles as potent anticancer and EGFR inhibitors

A general strategy was developed for the synthesis of new fully decorated 1,2,3-triazoles (5a-m & 6a-e) containing coumarine and sulfonyl-benzimidazole from 3-(2-((1-methyl-1H-benzo[d]imidazol-2-yl)sulfonyl)acetyl)-2H-chromen-2-one and several azides using Ramachary-Bressy-Wang organocatalytic cycloaddition method. In vitro anticancer activity of all these derivatives revealed that five compounds like 5f, 5j, 5k, 5l and 5m were active against three human cancer cell lines like breast carcinoma (MCF-7), cervical carcinoma (HeLa) and alveolar carcinoma (A-549). In specific, compounds 5k and 5m showed superior activity against MCF-7 and HeLa cell lines than the standard drugs Doxorubicin and Erlotinib. Later, the results of inhibitory assay of potent compounds 5f, 5j, 5k, 5l and 5m against the tyrosine kinase EGFR revealed that compounds 5k and 5m showed nearly double the potency of the reference drug erlotinib. The in silico studies of five potent compounds 5f, 5j, 5k, 5l and 5m were also carried out to identify the interactions against EGFR receptor and found that the energy calculations were covenant with the obtained IC50 values. Finally, in silico pharmacokinetic profile was predicted for five potent compounds using SWISS/ADME and pkCSM, where all the five compounds followed Lipinski and Veber rule without any deviation.

Development and optimization of curcumin analog nano-bilosomes using 21.31 full factorial design for anti-tumor profiles improvement in human hepatocellular carcinoma: in-vitro evaluation, in-vivo safety assay

Curcumin (CU) is a natural polyphenolic phytoingredient. CU has anti-inflammatory, anti-oxidant, and anticancer activities. The poor solubility, bioavailability, and stability of CU diminish its clinical application. Hence, structural modification of CU is highly recommended. The CU analog; 3,5-bis(4-bromobenzylidene)-1-propanoylpiperidin-4-one (PIP) exhibited high stability, safety, and more potent antiproliferative activity against hepatocellular carcinoma. In the present study, nano-bilosomes (BLs) were formulated to augment PIP delivery and enhance its solubility. A 21.31 full factorial design was adopted to prepare the synthesized PIP-loaded BLs. Optimized F4 showed a biphasic release pattern extended over 24 h, with EE%, ZP, and PS of 90.21 ± 1.0%, −27.05 ± 1.08 mV, and 111.68 ± 1.4 nm. PIP-loaded BLs were tested for safety against a non-cancerous cell line (Wi-38) and for anticancer activity against the Huh-7 human hepatocellular carcinoma cells and compared to the standard anticancer drug doxorubicin (Dox). The anticancer selectivity index of PIP-loaded BLs recorded 420.55 against Huh-7 liver cancer cells, markedly higher than a CU suspension (18.959) or the Dox (20.82). The antiproliferative activity of nano-encapsulated PIP was roughly equivalent to Dox. PIP-loaded BLs, showed enhanced drug solubility, and enhanced anticancer effect, with lower toxicity and higher selectivity against Huh-7 liver cancer cells, compared to the parent CU.

Anticancer Evaluation of Novel Quinazolinone Acetamides: Synthesis and Characterization.

According to the global cancer report 2019, the burden of cancer will exceed more than 18 million, becoming one of the major causes of global mortality rate. There is a pressing need to establish novel drug candidates for cancer treatment, though many anticancer agents are available in the market owing to their adverse effects. In recent years, quinazoline and its derivatives have been considered as a novel class of cancer chemotherapeutic agents that show promising activity against different tumors. To evaluate the anti-cancer potential of the novel class of quinazoline tethered acetamide derivatives against six different cancer cell lines. A novel series of various substituted quinazolinone acetamides were synthesized through a feasible scheme. The synthetic scheme involves the conversion of benzoxazinone (from anthranilic acid and benzoyl chloride) intermediate to 3-amino quinazoline-4-one which further converted to the final amide by tethering with the propionyl chloride employing Schotten-Baumann Reaction conditions. All the synthesized derivatives characterized by IR, 1HNMR and MASS spectral methods and anti-cancer activity were evaluated by employing MTT assay for six cancer cell lines and one normal human cell line. All the synthesized compounds were screened for anti-cancer activity against six cancer cell lines, including A 549 (lung), DU 145 (prostate), HT 29 (colon), MCF-7 (breast), SiHA (cervical), B16F10 (mouse skin melanoma) and one normal human fibroblast cell lines. All the compounds displayed a decent cytotoxicity profile when compared with the standard drug doxorubicin. Among the synthesized compounds (5a to 5n) tested, two compounds, 5f and 5g have demonstrated excellent cytotoxicity against SiHA and MCF-7 cancer cell lines. Comparatively most of the compounds displayed decent cytotoxicity potential relative to the standard drug doxorubicin. Further investigations are needed to establish the detailed mechanism of action of the developed novel quinazolinone acetamides.

Evaluation of apoptotic and anti-cancer efficacy of microwave assisted (ZnO-Ag2O) hybrid nanoparticles in MCF-7 breast cancer cell lines

The current study presents the synthesis and evaluation of zinc oxide and silver oxide hybrid nanoparticles for their potential apoptotic and anti-cancer activity. Owing to their small particle size, high surface area, and synergistic effects of embedded biomolecules, microwave-assisted synthesised nanoparticle-based drug delivery systems have significant potential in the field of biopharmaceutics and medicine. The higher activity of the hybrid nanoparticles may be attributed to their spherical shape, crystalline nature and lower particle size of 10–100 nm, as shown by different characterization methods as UV, FTIR, Zeta potential, particle size analysis, XRD, SEM, TEM, ICP-OES examination. The cell cycle analysis, cell death, and apoptosis in breast cancer cells (MCF-7) treated with synthesized hybrid NPs were evaluated in this work. Investigation of cell cycle analysis using flow cytometry has been utilized to analyse different phases of cell division and proliferation. The cytotoxic effect of microwave-assisted synthesised hybrid nanoparticles on MCF-7 cell line was studied using MTT assay and found to have significant cytotoxic activity with an IC50 value of 24.31 µg/ml when compared to standard drug Doxorubicin. Moreover, in vivo toxicity performed in Wistar rats reveals safety of developed hybrid nanoparticles. The findings demonstrate the powerful therapeutic efficacy of synthesized hybrid nanoparticles as well as the potential for development of future anticancer medication.

Synthesis, biological evaluation of novel thiopyrano[2,3-d]thiazoles incorporating arylsulfonate moiety as potential inhibitors of tubulin polymerization, and molecular modeling studies

Novel series of thiopyrano[2,3-d]1,3-thiazole derivatives incorporating arylsulfonate moiety were synthesized and characterized by 1H NMR, 13C NMR, MS, and IR. The synthesized compounds 6a–d, 8a–t, 10a–f, and 11a,b were evaluated for the cytotoxicity activity against four human cancer cell lines concerning mammary gland (MCF7), epithelioid carcinoma (Hela), human prostate cancer (PC3), and Hepatocellular carcinoma (HepG2). Compound 8d showed higher anticancer activity against MCF7 cell line (IC50 = 3.90 ± 0.4 µM) compared to the standard drug doxorubicin (IC50 = 4.17 ± 0.2 µM). Furthermore, compounds 6a has anticancer activity near to the standard drug doxorubicin against MCF7 and Hela cell lines with IC50 = 5.38 ± 0.6 µM, and 7.63 ± 0.8 µM, respectively. On the other hand, compound 8b exhibited an inhibitory effect against tubulin polymerization with an IC50 = 0.832 ± 0.031 µg/ml, which was similar to the positive control Colchicine (IC50 = 0.810 ± 0.10). The arylsulfonate moiety in 2,4-thiazolidinedithione core exerted a key effect on the anticancer activities of target compounds, according to structure-activity relationships (SARs) and docking studies. In HepG2 cells, compound 8b also caused cell cycle arrest at the G2/M phase and induced apoptosis.

Synthesis and biological evaluation of (4-Fluorophenyl)(1-(5-phenyl-1,3,4-oxadiazol-2-yl)indolizin-3-yl)methanone derivatives as anticancer and antimicrobial agents

A novel series of (4-Fluorophenyl (1-(5-phenyl-1,3,4-oxadiazol-2-yl)indolizin-3-yl)methanone derivatives 9(a-n) were synthesized by the coupling reaction of 3-(4-fluorobenzoyl)indolizine-1-carboxylic acid and substituted benzohydrazide followed by intramolecular cyclization. The structures of the compounds were characterized by 1H NMR, 13C NMR, LCMS, FT-IR, and elemental analyses. The compounds 9(a-n) anti-cancer activity was evaluated against the MCF-7 cell line (HTB-22, Homo sapiens, Breast carcinoma). Compound 9j (IC50 = 21.57 μM), and 9n (IC50 = 8.52 μM) exhibited the most potent cytotoxicity activity compared with standard drug doxorubicin (IC50= 25.71). The antibacterial activity was evaluated against Staphylococcus aureus ATCC 6538 and Escherichia coli ATCC 8739. The compounds ZOI=16mm) and 9i (ZOI=18 mm) exhibited moderate antibacterial activity compared with standard drug ciprofloxacin. The antifungal activity was evaluated against Candida albicans ATCC 10231. Most compounds exhibited moderate antifungal activity compared with the standard drug Itraconazole.

Role of Biosynthesized Ag-NPs Using Aspergillus niger (MK503444.1) in Antimicrobial, Anti-Cancer and Anti-Angiogenic Activities.

Green synthesis of nanoparticles is regarded as a safe and non-toxic process over conventional synthesis. Owing to the medicinal value of biologically derived biomolecules and utilizing them in synergy with nanoscience to offer more accurate therapeutic options to various diseases is an emerging field. One such study we present here with highlights of the synthesis and efficacy of biogenic silver nanoparticles produced from the extract of Aspergillus niger SAP2211 (accession number: MK503444.1) as an antimicrobial, anti-cancerous and anti-angiogenic agent. The synthesized Ag-NPs were characterized following UV–vis, FTIR, XRD, SEM and TEM, and were found to possess bactericidal activity against the selected pathogenic microbes, such as Staphylococcus aureus, Escherichia coli, and Salmonella typhi. Further, we evaluated cytotoxicity effect of this biogenic Ag-NPs using MMT assay on normal cardio myoblast (H9C2) and cancerous human cervical carcinoma (HeLa) cells. Doxorubicin used as positive control. This Ag-NPs have shown trivial cytotoxicity at the IC50 concentration on normal cells (IC50 = 47.17 µg/ml) over the cancer cells (IC50 = 8.609 µg/ml) with nearly 7 fold difference, indicating it as a selective anti-cancerous agent in contrast to standard drug doxorubicin (IC50 = 6.338 µg/ml). Further in-vitro assessment of wound healing capability by scratch wound healing assay, invasion by transwell matrigel invasion assay, and apoptosis via DAPI and annexin V-FITC assays were studied in HeLa cells. Synthesized biogenic Ag-NPs have shown to be anti-angiogenic in nature, which was established by in-vivo chick chorioallantois membrane assay. Overall, in vitro studies revealed that biogenic Ag-NPs positively inhibited migration, invasion, and induced apoptosis, and in-vivo CAM assay revealed that intercapillary network was reduced and the angiogenesis was inhibited.

Design, synthesis, cytotoxic and enzyme inhibitory activities of 1,3,4-oxadiazole and 1,3,4-thiadiazine hybrids against non-small cell lung cancer

Certain new 1,3,4-oxadiazole and 1,3,4-thiadiazine hybrids attached through thioacetamide linker (3a-p) were synthesized and tested in vitro for their cytotoxic activities towards a non-small cell lung cancer (NSCLC) cell line A549. The results indicated that eight compounds (3b, 3d, 3e, 3f, 3 g, 3 h, 3 k and 3n) exhibited more potent activity than the standard drug doxorubicin with IC50 range of 0.44 ± 0.02 – 2.84 ± 0.14 µM. Compound 3 g which displayed the highest cytotoxicity caught our interest for further investigation. It arrested the cell cycle at G2/M phase and showed proapoptotic action as reflected by Annexin-V-FITC assay. The activities of 3 g against certain enzymes which are reported to be overexpressed in NSCLC were studied. Promising inhibitory activities were demonstrated against vascular endothelial growth factor receptor2 (VEGFR2) (IC50 = 0.268 ± 0.006 µM), B-RAF (IC50 = 0.176 ± 0.009 µM), matrix metalloproteinases (MMPs) MMP1 (IC50 = 0.277 ± 0.006 µM) and MMP9 (0.084 ± 0.002 µM) with respect to corresponding reference drugs. Moreover, 3 g inhibited Telomerase activity by 36.55%. Docking study showed that 3 g bound to these target enzyme active sites similar to the co-crystallized ligands. Also, 3 g was more selective to A549 than WI-38 (a normal human fetal lung fibroblast cell line), with selectivity index (SI) = 59.79. In conclusion, 3 g is a promising multitarget anticancer compound which targets key pathways in NSCLC and requires further investigation.

In Vitro Cytotoxic activity of Rhinacanthin Enriched Extract from Leaves of Rhinacanthus nasutus (L.) Kurz., (Acanthaceae) against Neuroblastoma Cell Line

In the present study, the shade dried powdered leaves of Rhinacanthus nasutus (L.) Kurz., was subjected to maceration with ethyl acetate, concentrated and evaporated to dryness. The ethyl acetate extract was subjected to anion exchange column chromatography and the isolated rhinacanthin enriched extract was analyzed by thin layer chromatography and fourier-transform infrared studies. In the present study, the in vitro cytotoxic activity of the rhinacanthin rich extract of Rhinacanthus nasutus (L) Kurz., over SH-SY5Y human neuroblastoma cell line was assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-tetrazolium bromide assay and compared with the standard drug doxorubicin. The preliminary phytochemical screening revealed the presence of alkaloids, quinones, glycosides, carbohydrates, amino acids and tannins. The thin layer chromatography profiling showed the presence of secondary metabolites in various mobile phase systems. Fourier-Transform Infrared analysis of rhinacanthin enriched extract confirmed the presence of functional groups including 1, 4-quinone carbonyl component. The results of in vitro cell line studies revealed a dose dependent cytotoxic effect on human neuroblastoma cell lines with an IC50 value of 88.9 μg/ml. Thus the results validate the potential of rhinacanthin enriched extract against neuroblastoma cancer and based on this initial screening, further studies at elucidation of its molecular mechanism as cancer therapeutics can be undertaken.

Au-TiO2NANOSPHERES CATALYZED ONE-POT-MCR SYNTHESIS, CHARACTERIZATION AND ANTIPROLIFERATION ACTIVITY OF INDOLYL-IMIDAZOLOPYRIDINES CARBOXYLIC ACID HYBRIDS

In this context, we describe the efficiency of this catalyst towards green organic synthesis has been studied by carrying out a mixture of 1-fluoro-4-isocyanobenzene (1), 6-aminonicotinic acid (2)and substituted 1H-indole-3- carbaldehyde (3a-i) in distilled water, porous Au/TiO2nanospheres were added at room temperature in H2O. It proceeds yielding the corresponding isubstituted-3-((4-fluorophenyl) amino)-2-(1H-indol-3-yl)imidazo [1,2- a]pyridine-6-carboxylic acid derivative in good to excellent yield viz one-pot multi-component reaction. All the title compounds were also screened for Anti- proliferation activity screened for their in vitro anticancer activity against four human cancer cell lines MCF-7, HeLa, HEK 293T and IMR 32. Among them 4a (having 4-OCH3 substituent) has shown promising activity with IC50 (µM) 16.74±1.86 (MCF-7), 40.68 ± 1.25(HeLa), 50.61±4.64 (HEK 293T) and 26.58±1.68 (IMR32) has shown IC50 (µM) and these results are close to that of standard drug Doxorubicin.

First report on the synthesis and structural studies of trans-Phakellistatin 18: a rotamer of marine natural product phakellistatin 18

Phakellistatin peptides from marine organisms are the sources of proline-rich cyclic peptides with reported significant antitumor activities. Phakellistatin 18 (1), reported from marine sponge Phakellia fusca, contains three proline-peptide linkages in cis form. We attempted the total synthesis of natural product 1 through solution-phase macrocyclization approach, as a result, the synthetic cyclic peptide 2 was obtained as a rotamer of natural product having all three proline residues in trans-conformation. Here, we describe the synthesis, structural, and cytotoxicity studies of trans-Phakellistatin 18 (2), and its analog [Ala1,3,6]-Phakellistatin 18 (3). Detailed NMR studies were carried out to characterize the synthesized peptides, and anti-cancer screening was performed by using MTT assay. The synthetic trans-Phakellistatin 18 (2) (IC50=67.5 ± 2.938 µM) showed comparable cytotoxicity against HepG2 cancer cell line with standard drug doxorubicin (IC50=63.88 ± 6.48 µM). Here, the first synthetic and structural studies on trans-Phakellistatin 18 (2), and its anticancer screening against HepG2 cell line was reported.

Synthesis and Promising Cytotoxic Activity of Betulonic Acid Modified Derivatives

AbstractIn this paper, a series of betulonic acid N‐methylpiperazinyl amide derivatives, especially holding C2‐nicotinoylidene/furfurylidene/fluorobenzylidene fragments, have been synthesized and evaluated for their cytotoxic activity against the NCI‐60 cancer cell line panel. N‐Methylpiperazinyl amide of betulinic acid 11 (GI50=0.49 μM for leukemia CCRF‐CEM cell line), 2‐(4‐pyridinoylidene)‐betulinic 9 and betulonic 14 acids (GI50=1.60 and 1.36 μM for colon cancer HCT‐116 cell line, respectively), as well as 2‐(furfurylidene)‐betulonic acid 16 (GI50=1.66 μM for melanoma LOX IMVI cell line) were found to be the lead compounds. The activity displayed for these compounds was higher than for the standard drug doxorubicin against colon cancer HCT‐15 and ovarian cancer NCI/ADR‐RES cell lines. Cell cycle analysis indicates that compound 11 promotes cytotoxic activity through the apoptosis induction both in conditionally normal (HEK293) and in cancer (A549, MCF‐7) cells, whereas compound 14 exhibits both cytostatic and cytotoxic activity, dependently on cell line evaluated. In particular, in HEK293 cells the compound 14 induces mainly apoptotic cell death, while in A549 and MCF‐7 cells cytostatic effect is dependent on cell cycle arrest in the G2/M phase. Compounds 11 and 14 are promising molecules for future antitumor drug development.

Extraction and Isolation of Phenolic compounds from Sweet lime and Evaluation of Anticancer potentiality followed by Molecular docking against Topoisomerase II

The main aim and objective of the present research work was the isolation of some novel bioflavanoids from methanolic extract of peels of sweet lime (MEE-PSWL) and evaluation of in vitro anticancer activity followed by molecular docking against target protein topoisomerase II. The extraction was done by reflux condensation method and preliminary phytochemical screening of MEE-PSWL was carried out for the evaluation of bioactive molecules, the bioflavanoids present in MEE-PSWL was confirmed by spectral analysis such as ESI-MS-MS and FTIR. Molecular docking of isolated compounds was carried out against target protein Topoisomerase II with PDB id 1ZXM by Auto dock program and the best dock pose was selected based on the interaction study analysis. In vitro anticancer activity MEE-PSWL was evaluated by SRB assay toward human colon adenocarcinoma cell line SW620 and the test was carried out at different concentrations. A preliminary screening displayed that the MEE-PSWL was able to inhibit the proliferation of more than 60% of human colon adenocarcinoma SW620 cells. The maximum growth of inhibition was found to be at 125µg/ml (IC50 4.5µg/ml) and the standard drug doxorubicin was found to inhibit the maximum proliferation at concentration 75µg/ml (IC50 3µg/ml).