Facile Synthesis of 1,2-Disubstituted Benzimidazoles as Potent Cytotoxic Agents.

Benzimidazoles have a broad spectrum of biological and pharmacological properties, including anticancer activity. This study reports the facile synthesis and cytotoxic evaluation of twenty-eight 1,2-disubstituted benzimidazoles (6a-β), based on condensation reactions between N-benzyl o-phenylenediamine and benzylamine. The reactions were solvent-free, with the use of NaSO as an inexpensive and environmentally friendly oxidizing agent, and progressed rapidly.

Syntheses and Cytotoxicities of Quinazolinone-Based Conjugates.

Two novel series of quinazolinone-based hybrids, including quinazolinone-1,3,4-oxadiazoles (10a-l) and quinazolinone-1,3,4-oxadiazole-benzimidazoles (8a-e), were designed and synthesized and their cytotoxic activities against three human cancer cell lines, lung cancer (A549), cervical cancer (HeLa), and breast cancer (MCF-7), were evaluated. The cytotoxic assays revealed that 10i with a lipophilic 4-fluoro-phenyl moiety at the C-2 position of the quinazolinone ring displayed good cytotoxicities against the A549 and MCF-7 cell lines, while 8b-d with the thioether-linked benzimidazole moiety incorporated on the right side of the oxadiazole ring induced comparable stronger activities toward the MCF-7 cell line, relative to the simple two-heterocycle-containing hybrid 10i. These novel quinazolinone-based hybrids could be considered as lead compounds that merit further optimization and development as anti-cancer agents.

Target Design of Novel Histone Deacetylase 6 Selective Inhibitors with 2-Mercaptoquinazolinone as the Cap Moiety.

Epigenetic alterations found in all human cancers are promising targets for anticancer therapy. In this sense, histone deacetylase inhibitors (HDACIs) are interesting anticancer agents that play an important role in the epigenetic regulation of cancer cells. Here, we report 15 novel hydroxamic acid-based histone deacetylase inhibitors with quinazolinone core structures.