Novel pyrazolo[3,4-b]pyridine derivatives: Synthesis, characterization, antimicrobial and antiproliferative profile

Abstract

© 2016 The Pharmaceutical Society of Japan. Three novel series of pyridine derivatives, namely Schiff's bases, 4-thiazolidinones and azetidin-2-ones bearing pyrazolo[3,4-b]pyridine moiety, have been synthesized. The chemical structures of the synthesized compounds were characterized. The compounds were tested for their antimicrobial activity using the agar well diffusion and broth macrodilution methods. The compounds were also evaluated for their antiproliferative activity using the sulforhodamine B (SRB) assay. The majority of the tested compounds exhibited slight to high antimicrobial activity against the test microorganisms with minimum inhibitory concentrations (MICs) of 0.12-62.5 μg/mL when compared to that of 3 standard antimicrobial agents (Ampicillin, 0.007-0.03 μg/mL Gentamicin 0.015-0.24 μg/mL and Amphotericin B, 0.03-0.98 μg/mL). Compound (7b) was found to be nearly as active as the standard antimicrobial drug Amphotericin B against Fusarium oxysporum fungal strain with MIC of 0.98 μg/mL. Some of the test compounds showed remarkable cytotoxic activities against Hep G2 (hepatocellular carcinoma) cells (IC500.0158-71.3 μM) in comparison to the standard anticancer drug doxorubicin (IC500.008 μM). Among the compounds tested, (5), (6a), (6b), (7b), and (10) exhibited antiproliferative potency (IC500.0001-0.0211 μM) that was found to be better than that of doxorubicin (IC500.099 μM) against MCF7 (breast adenocarcinoma) cells. In particular, (7b) displayed the highest significant antiproliferative efficacy against both Hep G2 and MCF7 cell lines showing IC50 values of 0.0158 μM and 0.0001 μM, respectively. Our findings suggest that the synthesized compounds may be promising candidates as novel antimicrobial and antiproliferative agents.