Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Alexandria, Alexandria 21521, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy & Drug Manufacturing, Pharos University in Alexandria, Alexandria, Egypt.
Department of Pharmaceutical Sciences, Faculty of Pharmacy, Beirut Arab University, Beirut, Lebanon.
Bioorg Chem. 2019 Jul;88:102934. doi: 10.1016/j.bioorg.2019.102934. Epub 2019 Apr 16.
In continuation of our research program aiming at developing new potent antimicrobial agents, new series of substituted 3,4-dihydrothieno[2,3-d]pyrimidines was synthesized. The newly synthesized compounds were preliminary tested for their in vitro activity against six bacterial and three fungal strains using the agar diffusion technique. The results revealed that compounds 7, 8a, 10b, 10d and 11b exhibited half the potency of levofloxacine against the Gram-negative bacterium, Pseudomonas aeruginosa, while compounds 5a, 8b, 10c and 12 displayed half the potency of levofloxacine against Proteus Vulgaris. Whereas, compounds 7, 10b, 10d and 11b showed half the activity of ampicillin against the Gram-positive bacterium, B. subtilis. Most of the compounds showed high antifungal potency. Compounds 3, 6, 7, 9b, 10a, 11a, 11b, 15 and 16 exhibited double the potency of clotrimazole against A. fumigatus. While compounds 3, 4, 5a, 5b, 9b, 10a, 10b, 10c, 13, 15, 16 and 18 displayed double the activity of clotrimazole against R. oryazae. Molecular docking studies of the active compounds with the active site of the B. anthracis DHPS, showed good scoring for various interactions with the active site of the enzyme compared to the co-crystallized ligand.
在我们旨在开发新型强效抗菌剂的研究计划续集中，合成了一系列新的取代 3,4-二氢噻吩并[2,3-d]嘧啶。使用琼脂扩散技术，初步测试了新合成的化合物对六种细菌和三种真菌菌株的体外活性。结果表明，化合物 7、8a、10b、10d 和 11b 对革兰氏阴性菌铜绿假单胞菌的活性为左氧氟沙星的一半，而化合物 5a、8b、10c 和 12 对普通变形杆菌的活性为左氧氟沙星的一半。然而，化合物 7、10b、10d 和 11b 对革兰氏阳性菌枯草芽孢杆菌的活性为氨苄西林的一半。大多数化合物表现出很高的抗真菌活性。化合物 3、6、7、9b、10a、11a、11b、15 和 16 对烟曲霉的活性为克霉唑的两倍。而化合物 3、4、5a、5b、9b、10a、10b、10c、13、15、16 和 18 对梨孢镰刀菌的活性为克霉唑的两倍。与炭疽杆菌 DHPS 的活性部位进行的活性化合物的分子对接研究表明，与酶的活性部位相比，与结合配体相比，各种相互作用的评分都很好。
