Khwaza Vuyolwethu, Oyedeji Opeoluwa O, Oselusi Samson O, Morifi Eric, Nwamadi Mutshinyalo, Tantoh Ndinteh Derek, Ramushu P, Matsebatlela Thabe, Aderibigbe Blessing A
Department of Chemistry, University of Fort Hare, Alice Campus, Alice, Eastern Cape, South Africa.
School of Pharmacy, University of the Western Cape, Bellville, Cape Town, 7535, South Africa.
Chem Biodivers. 2023 Apr;20(4):e202300034. doi: 10.1002/cbdv.202300034. Epub 2023 Mar 28.
The molecular hybridization of two or more drugs into a single molecule is an effective drug design approach to reduce pill burden and improve patient treatment adherence. Ursolic acid-based hybrid compounds were synthesized and characterized followed by molecular docking studies. In vitro studies against various bacterial strains and human cancer cells (MDA-MB-231, HeLa, and MCF-7) were performed. Compounds 14-19, 21, 34, 31, and 30 demonstrated significant antibacterial activities with MIC values of 15.625 μg/ml. Compounds 29 and 34 were more cytotoxic than ursolic acid, with IC values of 46.99 and 48.18 μg/ml. Compounds 29 and 34 in the docking studies presented favourable binding interactions and better docking energy against the Epidermal Growth Factor Receptor (EGFR) than the parent compound, ursolic acid. The findings revealed that the ursolic acid scaffold is a promising precursor for the development of molecules with promising anticancer and antimicrobial activities. However, more studies are needed to fully understand their mode of action.
将两种或更多种药物分子杂交成单一分子是一种有效的药物设计方法，可减轻服药负担并提高患者治疗依从性。合成并表征了基于熊果酸的杂化化合物，随后进行了分子对接研究。针对各种细菌菌株和人类癌细胞（MDA-MB-231、HeLa和MCF-7）开展了体外研究。化合物14-19、21、34、31和30表现出显著的抗菌活性，最低抑菌浓度（MIC）值为15.625μg/ml。化合物29和34比熊果酸具有更强的细胞毒性，半数抑制浓度（IC）值分别为46.99和48.18μg/ml。在对接研究中，化合物29和34与表皮生长因子受体（EGFR）呈现出比母体化合物熊果酸更有利的结合相互作用和更好的对接能量。研究结果表明，熊果酸支架是开发具有潜在抗癌和抗菌活性分子的有前景的前体。然而，需要更多研究来充分了解它们的作用方式。
