Design,Synthesis And Anticancer Activity Of Novel Benzimidazole And Benzoxazole Derivatives

Backgound and Purpose:Designing and synthesizing high-efficiency and low-toxicity anti-cancer drugs is the current research hotspot.In this project,we use diverse biological benzimidazole and benzoxazole scaffold as start materials,designed and synthesized novel benzimidazole and benzoxazole derivatives.The antiproliferative activities of these compounds were evaluated to obtained high high-efficiency and low-toxicity anti-cancer drugs.Methods:Within the past ten years,a huge volume of research on the synthesis,structure-activity relationships(SAR),and anticancer activities of the thiourea and urea derivatives were reported.Thus,in this project,30 novel benzimidazole and benzoxazole thiourea and urea derivatives were design and synthesized,the chemical structUres of these compounds were determined by 1H-NMR and ESI-MS.The antiproliferative activities of these compounds were evaluated against seven human tumor cell lines(hepatocellular carcinoma line HEP-G2,gastric cancer line SGC7901,lung cancer line A549,breast cancer line MCF-7,colon cancer line HCT116,pancreatic cancer line Panc-1 and cervical cancer cell line Hela)by applying the MTT colorimetric assay.Analysis of apoptosis induced by compounds D8 in the HCT116 cancer cell line was also been evaluated.Results and conclusion:In this project,18 benzimidazole thiourea and urea derivatives,12 benzoxazole thiourea derivatives were designed and synthesized.The compounds were assayed for antiproliferative activities against the(hepatocellular carcinoma line HEP-G2,gastric cancer line SGC7901,lung cancer line A549,breast cancer line MCF-7,colon cancer line HCT116,pancreatic cancer line Panc-1 and cervical cancer cell line Hela by MTT(3-(4,5-dimethylthyithiazol-2-yl)-2,5-diphenyltetrazolium bromide)method.Among them,benzimidazole thiourea derivatives showed more potent anticancer activities than benzoxazole thiourea derivatives,C7?C8?C10?C11?C13 and C14 showed potent activities and selectivity against colon cancer line HCT116(D8 and C14 IC50 7.4 and 5.2?M,respectively).It is hoped that increasing knowledge of the SAR and cellular processes underlying the antitumor-activity of urea derivatives will be beneficial to the rational design of new generation of urea anticancer drugs.