Designed, synthesized a series of novel imidazo[1,2-a]pyridine derivatives and evaluated for their in vitro cytotoxicity. Fluorine containing compounds, (2-fluorophenyl)(4-(2-(pyridin-2-yl)imidazo[1,2-a]pyridin-6-yl)piperazin-1-yl)methanone (7 e),(4-(2-(pyridin-2-yl)imidazo[1,2-a]pyridin-6-yl)piperazin-1-yl)(2-(trifluoromethyl)phenyl)methanone (7 h) and (3-fluorophenyl) (4-(2-(pyridin-2-yl)imidazo[1,2-a]pyridin-6-yl)piperazin-1-yl)methanone (7 i) were found to have an effective cytotoxic profile against HepG2, HeLa and MDA-MB-231. Compounds 7 h (IC 50 = 5.8 μM) and 7 i (IC 50 = 3.5 μM) were found potent when compared with control Paclitaxel (IC 50 = 2.8 μM), against HeLa. Compound 7 h also found to be potent against HepG2 (IC 50 = 2.0 μM) and MDAMB-231(IC 50 = 6.9 μM) respectively, when compared with Paclitaxel (HepG2, IC 50 = 0.56 μM; MDAMB-231, IC 50 = 1.9 μM). Compound 7 e also found to be potent against HepG2 (IC 50 = 9.8 μM) cell lines. Synthesized piperazine linked imidazo[1,2-a]pyridine derivatives (7 i, IC 50 = 3.5 μM) and (7 h, IC 50 = 5.8 μM) showed 1.74 fold, 1.12 fold increase in antiproliferative activity than reported homopiperazine linked imidazo [1,2-a]pyrimidine derivatives (4-Fluorophenyl)(4-(2-(4fluorophenyl)imidazo[1,2-a]pyrimidin-7-yl)-1,4-diazepan-1-yl)methanone(10 f, IC 50 = 6.12 μM) and (4-(2-(4-Fluorophenyl)imidazo[1,2-a]pyrimidin-7-yl)-1,4-diazepan-1-yl)(3methoxyphenyl)methanone (12, IC 50 = 6.54 μM) against Hela cell lines. Molecular docking studies showed that designed compounds occupy at the active site of both colchicine and human estrogen receptor which demonstrated that the designed compounds were able to bind with multiple targets, the biological activity of these compounds hold promise to find application in considering for treatment protocol.[a] M.
A series of 2‐mercapto benzothiazole linked with triazoles (3 a‐u) were designed based on our previous experimental evaluation of benzothiazole allied oxadiazoles and synthesized in two step starting from the 2‐mercaptan precursor. The structure of the benzothiazoles were confirmed by infrared (IR), nuclear magnetic resonance (NMR) and mass (LC–MS) spectral data. The insilico binding mode interpretations in both COX‐1/COX‐2 was investigated, their probable binding energies were predicted and ADMET properties were calculated. The molecular level interactions of the designed library indicated, the aryl ring united with triazole was occupying as mefenamic acid in COX‐2 active site. All the benzothiazoles 3 a‐u were evaluated for their COX inhibitory activities as per the standard protocol reported elsewhere. 2‐(((1‐(2‐chlorobenzyl)‐1H‐1,2,3‐triazol‐4‐yl)methyl)thio)benzo[d]thiazole 3 i, 4‐((4‐((benzo[d]thiazol‐2‐ylthio)methyl)‐1H‐1,2,3‐triazol‐1‐yl)methyl)benzoic acid 3 t and 4‐((4‐((benzo[d]thiazol‐2‐ylthio)methyl)‐1H‐1,2,3‐triazol‐1‐yl)methyl)benzamide 3 u based benzthiazoles showed the most significant COX‐2 inhibitory activity with an IC50 of 4.1, 4.3 and 5.4 μM respectively. The time dependant increase in inhibition of inflammation of above COX‐2 inhibitors in invivo anti‐inflammatory evaluation was noticed. Additionally, 2‐(((1‐(3‐fluorobenzyl)‐1H‐1,2,3‐triazol‐4‐yl)methyl)thio)benzo[d]thiazole 3 g expressed the significant DPPH scavenging activity with 80.45 percent inhibition at 100 μM and an IC50 of 27.8 μM. Furthermore, the 50 ns molecular dynamic simulations of 2‐(((1‐(2‐chlorobenzyl)‐1H‐1,2,3‐triazol‐4‐yl)methyl)thio)benzo[d]thiazole 3 i to interpret the constant residue interactions might liable for the COX selectivity was presented. Later, they also have been tested for cancer lines at NCI and obtained data were provided.
Spirooxindole motifs found in many natural products and biologically active molecules have become important skeletons given their promising therapeutic activities. In this study, we describe the synthesis of a novel series of spiro [piperidine-4,3'pyrrolo[2,3-b]pyridin]-2'(1'h)-one analogues and present the in vitro antiproliferative activity of these compounds against four human cancer cell lines. Synthesis of analogues was done using a rational designing approach in a seven-step sequence, and the characterization of compounds was performed using 1 H-NMR, LC-MS, and 13 C-NMR. Thirteen novel compounds were synthesized in moderate to good yields. The anti-proliferation activity of the compounds against human breast MCF-7 and MDA-MB-231, leukemic K-562, and lung A549 cancer cells was determined by a standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay. Two compounds among all the synthesized compounds had moderate IC 50 values in MCF-7 cells and thus were identified to have better antiproliferative activity against estrogen-receptor-positive cancer cells.
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