Razzaghi-Asl Nima, Kamrani-Moghadam Mahsa, Farhangi Behzad, Vahabpour Rouhollah, Zabihollahi Rezvan, Sepehri Saghi
Department of Medicinal Chemistry, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, I.R. Iran.
Medical Lab Technology Department, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, I.R. Iran.
Res Pharm Sci. 2019 Mar 8;14(2):155-166. doi: 10.4103/1735-5362.253363. eCollection 2019 Apr.
A series of new 1,2,3,4-tetrahydropyrimidine (THPM) derivatives were designed and synthesized within a one-pot three component Biginelli reaction. The structures of compounds were characterized by FT-IR, 1HNMR, mass spectroscopy, and elemental analysis. All synthesized derivatives were screened for their cytotoxic, antimicrobial, and anti-HIV activities. Due to significant cytotoxic and antimicrobial effects of 1,2,3,4-THPM scaffold, in this study, cytotoxic and antimicrobial activities of synthesized derivatives were evaluated on two cell lines and four bacterial strains. Compounds and showed highest cytotoxic activity against HeLa and MCF-7 cell lines. In addition, and were most active against MCF-7 and HeLa cell lines, respectively. Among the compounds, revealed high antimicrobial activity against four strains. According to the results, 4e possessing -bromophenyl group at C-4 position of THPM exhibited the highest cytotoxic and antimicrobial effects. Also, all the newly synthesized compounds were evaluated for their anti-HIV-1 assay. Compounds and indicated remarkable anti-HIV-1 activity. It is concluded from cytotoxic, antimicrobial, and anti-HIV-1 activities that the 1,2,3,4-tertahydropyrimidines may serve as hit compounds for development of new anticancer small-molecules.
通过一锅三组分Biginelli反应设计并合成了一系列新型1,2,3,4-四氢嘧啶（THPM）衍生物。通过傅里叶变换红外光谱（FT-IR）、核磁共振氢谱（1HNMR）、质谱和元素分析对化合物的结构进行了表征。对所有合成的衍生物进行了细胞毒性、抗菌和抗HIV活性筛选。由于1,2,3,4-THPM骨架具有显著的细胞毒性和抗菌作用，在本研究中，在两种细胞系和四种细菌菌株上评估了合成衍生物的细胞毒性和抗菌活性。化合物 和 对HeLa和MCF-7细胞系表现出最高的细胞毒性活性。此外， 和 分别对MCF-7和HeLa细胞系最具活性。在这些化合物中， 对四种菌株显示出高抗菌活性。根据结果，在THPM的C-4位带有 -溴苯基的4e表现出最高的细胞毒性和抗菌作用。此外，对所有新合成的化合物进行了抗HIV-1检测。化合物 和 显示出显著的抗HIV-1活性。从细胞毒性、抗菌和抗HIV-1活性得出结论，1,2,3,4-四氢嘧啶可能作为开发新型抗癌小分子的先导化合物。
