Cytotoxic Effects of Newly Synthesized Heterocyclic Candidates Containing Nicotinonitrile and Pyrazole Moieties on Hepatocellular and Cervical Carcinomas

Abstract

In this study, a series of newly synthesized substituted pyridine 9, 11–18, naphthpyridine derivative 10 and substituted pyrazolopyridines 19–23 by using cycnopyridone 8 as a starting material. Some of the synthesized candidates are evaluated as anticancer agents against different cancer cell lines. In vitro cytotoxic activities against hepatocellular and cervical carcinoma cell lines were evaluated using standard MTT assay. Different synthesized compounds exhibited potential in vitro cytotoxic activities against both HepG2 and HeLa cell lines. Furthermore, compared to standard positive control drugs, compounds 13 and 19 showed the most potent cytotoxic effect with IC50 values of 8.78 ± 0.7, 5.16 ± 0.4 μg/mL, and 15.32 ± 1.2 and 4.26 ± 0.3 μg/mL for HepG2 and HeLa cells, respectively.

Antiproliferative Activity of Some Newly Synthesized Substituted Pyridine Candidates Using 4-(Aaryl)-6-(naphthalen-1-yl)-2-oxo-1,2-dihydropyridine-3-carbonitrile as Synthon

“…In our increasing interest in ethyl cyanoacetate as well as synthesis of pyridones, 12 we would like to report a mild, cost-effective procedure for the one-pot multicomponent syntheses of 4-(4-chlorophenyl)-6-(naphthalen-1-yl)-2-oxo-1,2-dihydropyridine-3-carbonitrile and 6-(naphthalen-1-yl)-2-oxo-4-(thiophen-2-yl)-1,2-dihydropyridine-3-carbonitrile ( 4a , b ) by the condensation of aldehydes, namely, 4-chlorobenzaldehydeor thiophene-2-carboxaldehyde, respectively, 1-(naphthalen-1-yl)ethanone and ethyl cyanoacetate, in the presence of a catalytic amount of ammonium acetate and drops of piperidine at ambient temperature in an ethanol medium ( Scheme 1 ). The structures of nicotinonitriles 4a , b were confirmed by their spectral and elemental analyses.…”

“…Chemistry. In our increasing interest in ethyl cyanoacetate as well as synthesis of pyridones, 12 we would like to report a mild, cost-effective procedure for the one-pot multicomponent syntheses of 4-( 4 In an attempt to prepare certain novel heterocycles, 19−21 determine their insecticidal effectiveness, 22−24 and evaluate their pharmaceutical significance, 25−28 compounds 4a,b were allowed to react with phenylisothiocyanate to yield 4-…”

“…Nicotinonitrile derivatives containing the 2-naphthyl moiety 1a , b showed cytotoxic activity against McF-7 and HEPG2 . Nicotinonitrile derivatives containing the pyrazole moiety 2a , b also showed a significant cytotoxic activity against hepatocellular and cervical carcinomas . Novel fused nicotinonitrile derivatives 3a , b were constructed and evaluated as anticancer agents against NCI-H460, MCF-7, and SF-268 cell lines (Figure ).…”

“…for C 26 H 17 ClN 4 O (436.11): C, 71.48; H, 3.92; N, 12.82. Found C, 71.51; H, 3.95; N,12.83%. To a solution of hydrazides (11a,b) (0.5 g, 0.001 mol) in dry pyridine (10 mL), phenylacetyl chloride (0.2 mL, 0.001 mol) was added.…”

Pyridine‐2(1H)‐thiones: Versatile precursors for one‐pot synthesis of new nicotinonitrile‐thiazole hybrids

“…They also act as potent inhibitors of dipeptidyl peptidase-IV [34], acetylcholinesterase [39,40], and COX-2 enzymes [24]. Some biologically active hybrids linked to nicotinonitrile units are presented in Figure 2 [24,[40][41][42].…”