New approaches for the synthesis, cytotoxicity and toxicity of heterocyclic compounds derived from 2-cyanomethyl benzo[c]imidazole

Abstract

The reaction of ethyl cyanoacetate with o-phenylenediamine gave the 2-cyanomethylbenzo[c]imidazole (1). The latter compound was used as the key starting material to synthesise biologically active heterocyclic derivatives. Thus, the reaction of 1 with cyclohexanone and either of benzaldehyde, 4-methoxybenzaldehyde or 4-chlorobenzaldehyde gave the annulated derivatives 2a-c, respectively. The antitumor evaluations of the newly synthesized products against the three cancer cell lines MCF-7 (breast adeno-carcinoma), NCI-H460 (non-small cell lung cancer) and SF-268 (CNS cancer) showed that compounds 2b, 6, 11b, 11c, 12b, 16a, 16b and 18a exhibited optimal cytotoxic effect against cancer cell lines, with IC 50 values in the nM range. Bioactive compounds are often toxic to shrimp larvae. Thus, in order to monitor these chemicals in vivo lethality to shrimp larvae (Artemia salina), Brine-Shrimp Lethality Assay was used. Compounds 11b, 12b and 16b showed no toxicity against the tested organisms.

Design, Synthesis and In Vitro Cytotoxic Activity of New 6,9-Disubstituted Purine Analogues

“…In addition to this, various heterocyclic analogs of purines, such as imidazo-pyrazines, 39 pyrazolo-pyridazines, 40 imidazo-pyridines, 41,42 thieno-pyridines, 43 pyrrolo-pyrimidines, 44 pyrazolo-pyrimidines, 45,46 thieno-pyrimidines 47 and triazolo-pyrimidines 48,49 have been found to possess anticancer activities.…”

Anti-inflammatory and Anti-ulcer Activities of New Fused Thiazole Derivatives Derived from 2-(2-Oxo-2H-chromen-3-yl)thiazol-4(5H)-one

“…Thiazole derivatives also exhibit a broad spectrum of medicinal and biological properties, such as antibacterial, antifungal, 1 anti-inflammatory, 2 antiviral, In many report structural modification of the heterocyclic rings through the construction of new heterocyclic nuclei enhances the pharmaceutical applications of the resulting molecules. 15,16 This encouraged our efforts in this work to modify 2-(4-oxo-4,5-dihydrothiazol-2-yl)acetonitrile through its reaction with salicyladehyde to produce a chromen-3-yl)thiazol which was used as the key starting compound for many further heterocyclic transformations. The anti-inflammatory and anti-ulcer evaluations of the newly synthesized compounds were studied.…”

Synthesis of Some Substituted 6-Phenyl Purine Analogues and Their Biological Evaluation as Cytotoxic Agents

“…[1][2][3][4] Potent purine-based cyclin-dependent kinase inhibitors olomoucine, 5 roscovitine, 6 purvalanol A, B, amino-purvalanol 7 ( Fig. 2) and heterocyclic analogues of these compounds imidazo-pyrazines, 8 pyrazolo-pyrida- zines, 9 imidazo-pyridines, 10,11 thieno-pyridines, 12 pyrrolo-pyrimidines, 13 pyrazolo-pyrimidines 14,15 and triazolopyrimidines 16,17 have been investigated as anticancer agents.…”