Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa.
SAMRC/NHLS/UCT Molecular Mycobacteriology Research Unit, Department of Pathology, University of Cape Town, Observatory, South Africa.
Chem Biol Drug Des. 2023 Mar;101(3):717-726. doi: 10.1111/cbdd.14174. Epub 2022 Nov 17.
Curcumin is a natural product that has been reported to exhibit myriad pharmacological properties, one of which is antitubercular activity. It demonstrates antitubercular activity by directly inhibiting Mycobacterium tuberculosis (M.tb) and also enhances immune responses that ultimately lead to the elimination of M.tb by macrophages. This natural product is, however, unstable, and several analogues, noticeably monocarbonyl analogues, have been synthesized to overcome this challenge. Curcumin and its monocarbonyl analogues reported so far exhibit moderate antitubercular activity in the range of 7 to 16 μM. Herein, we report a straightforward synthesis of novel monocarbonyl curcumin analogues, their antitubercular activity, and the structure-activity relationship. The hit compound from this study, 3a, exhibits potent MIC values in the range of 0.2 to 0.9 μM in both ADC and CAS media.
姜黄素是一种天然产物，据报道具有多种药理特性，其中之一是抗结核活性。它通过直接抑制结核分枝杆菌（M.tb）来发挥抗结核活性，同时增强免疫反应，最终导致巨噬细胞清除 M.tb。然而，这种天然产物不稳定，已经合成了几种类似物，特别是单羰基类似物，以克服这一挑战。迄今为止报道的姜黄素及其单羰基类似物在 7 至 16 μM 的范围内表现出中等的抗结核活性。在此，我们报告了一种新型单羰基姜黄素类似物的简便合成方法，及其抗结核活性和构效关系。本研究中的命中化合物 3a 在 ADC 和 CAS 培养基中均表现出 0.2 至 0.9 μM 的强效 MIC 值。
