Synthesis and cytotoxicity evaluation of novel cyclic/non-cyclic N-aryl enamino amides against human cancer cell lines.

BACKGROUND AND PURPOSE: Considering the undesirable consequences of prevalent cancer diseases, design and development of potent and selective anticancer chemotherapeutics is a major concern. Several studies have unraveled the potential of dihydropyrimidinone (DHPM) scaffold toward generating anticancer agents. EXPERIMENTAL APPROACH: In the present work, a series of new dihydropyrimidinethiones (DHPMTs) along with a few acyclic enamino amides were synthesized and evaluated for their cytotoxic activity against human gastric (AGS), liver (Hep-G2), and breast (MCF-7) cancer cell lines. FINDINGS/RESULTS: Among the assessed compounds, one of the DHPMT derivatives (compounds, one of the DHPMT derivatives (compound 5: 4-(3- fluorophenyl)-6-methyl-N-phenyl-2-thioxo-1,2,3,4-ttrahydropyrimidine-5-carboxamide) exhibited superior cytotoxicity in all of the target cell lines (AGS, IC50 9.9 µM; MCF-7, IC50 15.2 µM; and Hep-G2, IC50 40.5 µM). Cytotoxicity assessments showed that non-cyclic enamino amides exhibited weaker activities when compared to cyclic analogues (DHPMs). CONCLUSION AND IMPLICATIONS: DHPMTs were better cytotoxic agents than non-cyclic enamino amides. Structure activity relationship studies guided us toward the design of DHPMT derivatives with OH and NH groups particularly on meta position of 4-phenyl ring and hydrophobic bulky substituents on carboxamide side chain within the structure. Possible interaction with the hydrophobic site(s) of the cellular target was supposed. The results of this study emphasized the potential role of DHPMTs and their optimized derivatives as privileged medicinal scaffolds to inhibit the growth of gastric, breast, and liver cancer cells.

Insights into the current status of privileged N-heterocycles as antileishmanial agents.

Leishmania, one of the most important neglected tropical diseases, is endemic in several regions of the world and hence regarded as a serious threat to public health. Major difficulties with current chemotherapeutic agents raise issues such as toxicity, resistance, cost and other side effects. These issues necessitate development of potentially new chemical entities against diverse leishmanial species. Numerous natural and synthetic new antileishmanial molecules have been described for disease management. Careful inspection of scientific reports revealed that considerable amount of promising antileishmanial agents belonged to the nitrogen-containing heterocycles such as quinoline, triazole, pyrazole, imidazole, indole, pyrimidine, ß-carboline, quinoxaline, quinazoline and benzimidazole. In this regard, enormous chemical data provide the opportunity for systematic elucidation of structural requirements against different leishmanial species. Within this representation, insights into the current status of privileged N-heterocycles as antileishmanial agents with particular emphasis on structure activity relationships are reviewed.