Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
Laboratory of Research in Pharmaceutical Chemistry, Department of Food and Drugs, Faculty of Pharmaceutical Sciences, Federal University of Alfenas, Rua Gabriel Monteiro da Silva 700, Alfenas 37130-001, Brazil.
Mar Drugs. 2023 Oct 24;21(11):551. doi: 10.3390/md21110551.
Natural products are a very rich source for obtaining new compounds with therapeutic potential. In the search for new antiparasitic and antimicrobial agents, molecular hybrids were designed based on the structures of antimicrobial marine quinazolinones and eugenol, a natural phenolic compound. Following reports of the therapeutic potential of quinazolinones and eugenol derivatives, it was expected that the union of these pharmacophores could generate biologically relevant substances. The designed compounds were obtained by classical synthetic procedures and were characterized by routine spectrometric techniques. Nine intermediates and final products were then evaluated in vitro against and . Antifungal and antibacterial activity were also evaluated. Six compounds (, , , , , and ) showed mild activity against with IC in the range of 11.17-31.68 μM. Additionally, intermediate showed anti- activity (IC 7.54 μM) and was six times less cytotoxic against THP-1 cells. In conclusion, novel derivatives with a simple quinazolinone scaffold showing selectivity against parasites without antibacterial and antifungal activities were disclosed, paving the way for new antitrypanosomal agents.
天然产物是获得具有治疗潜力的新化合物的非常丰富的来源。在寻找新的抗寄生虫和抗菌药物时，基于抗菌海洋喹唑啉酮和天然酚类化合物丁香酚的结构设计了分子杂合体。在报道了喹唑啉酮和丁香酚衍生物的治疗潜力之后，人们期望这些药效团的结合可以产生具有生物学相关性的物质。通过经典的合成程序获得设计的化合物，并通过常规光谱技术进行了表征。然后对 9 个中间体和最终产物进行了体外抗 和 的活性评价。还评估了抗真菌和抗菌活性。有 6 种化合物（、、、、、和 ）对 表现出温和的活性，IC 在 11.17-31.68 μM 范围内。此外，中间体 表现出抗 活性（IC 7.54 μM），对 THP-1 细胞的细胞毒性低 6 倍。总之，揭示了具有简单喹唑啉酮支架的新型衍生物对寄生虫具有选择性而没有抗菌和抗真菌活性，为新型抗锥虫药物开辟了道路。
