Synthesis and in vitro anticancer activity of certain novel 1-(2-methyl-6-arylpyridin-3-yl)-3-phenylureas as apoptosis-inducing agents

Journal of Enzyme Inhibition and Medicinal Chemistry

Hatem A. Abdel-Aziz¹  Tarfah Al-Warhi²  Ahmed E. Altyar³  Ghada S. Hassan⁴  Abdulrahman A. Almehizia⁵  Sara T. Al-Rashood⁵  Hamad M. Alkahtani⁵  Wagdy M. Eldehna⁶ 

[1]Department of Applied Organic Chemistry, National Research Center, Cairo, Egyp

[2]Department of Chemistry, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia

[3]Department of Clinical Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia

[4]Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt

[5]Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia

[6]Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt

关键词: Anticancer agents;    apoptosis;    cell cycle;    pyridine-urea;    synthesis;   

DOI  :  10.1080/14756366.2018.1547286

来源: publisher

【 摘 要 】

In connection with our research program on the development of novel anticancer candidates, herein we report the design and synthesis of novel series of 1-(2-methyl-6-arylpyridin-3-yl)-3-phenylureas 5a–l. The target pyridins were evaluated for their in vitro anticancer activity against two cancer cell lines: non-small cell lung cancer A549 cell line and colon cancer HCT-116 cell line. Compound 5l emerged as the most active congener towards both A549 and HCT-116 cell lines with IC50 values equal to 3.22 ± 0.2 and 2.71 ± 0.16 µM, respectively, which are comparable to those of Doxorubicin; 2.93 ± 0.28 and 3.10 ± 0.22, respectively. Furthermore, compound 5l stood out as the most potent pyridine derivative (mean % GI = 40), at US-NCI Developmental Therapeutic Program anticancer assay, with broad-spectrum antitumor activity against the most tested cancer cell lines from all subpanels. Compound 5l was able to provoke apoptosis in HCT-116 cells as evidenced by the decreased expression of the anti-apoptotic Bcl-2 protein, and the enhanced expression of the pro-apoptotic proteins levels; Bax, cytochrome C, p53, caspase-3 and caspase-9. Moreover, 5l disrupted the HCT-116 cell cycle via alteration of the Sub-G1 phase and arresting the G2-M stage. Also, 5l showed a significant increase in the percent of annexinV-FITC positive apoptotic cells from 1.99 to 15.76%.

【 授权许可】

CC BY