Department of clinical pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 31441, Dammam, Saudi Arabia.
Department of Chemistry, Hazara University, Mansehra, 21300, Khyber Pakhtunkhwa, Pakistan.
Sci Rep. 2020 May 14;10(1):7969. doi: 10.1038/s41598-020-64729-3.
The current study describes synthesis of diindolylmethane (DIM) derivatives based-thiadiazole as a new class of urease inhibitors. Diindolylmethane is natural product alkaloid reported to use in medicinal chemistry extensively. Diindolylmethane-based-thiadiazole analogs (1-18) were synthesized and characterized by various spectroscopic techniques HNMR, C-NMR, EI-MS and evaluated for urease (jack bean urease) inhibitory potential. All compounds showed excellent to moderate inhibitory potential having IC value within the range of 0.50 ± 0.01 to 33.20 ± 1.20 µM compared with the standard thiourea (21.60 ± 0.70 µM). Compound 8 (IC = 0.50 ± 0.01 µM) was the most potent inhibitor amongst all derivatives. Structure-activity relationships have been established for all compounds. The key binding interactions of most active compounds with enzyme were confirmed through molecular docking studies.
本研究描述了基于二吲哚甲烷（DIM）的噻二唑衍生物的合成，这是一类新的脲酶抑制剂。二吲哚甲烷是一种天然产物生物碱，在药物化学中被广泛应用。通过各种光谱技术 HNMR、C-NMR、EI-MS 对基于二吲哚甲烷的噻二唑类似物（1-18）进行了合成和表征，并评估了它们对脲酶（豆类脲酶）的抑制潜力。与标准硫脲（21.60±0.70µM）相比，所有化合物均表现出优异到中等的抑制潜力，IC 值范围为 0.50±0.01 至 33.20±1.20µM。所有衍生物中，化合物 8（IC=0.50±0.01µM）是最有效的抑制剂。建立了所有化合物的构效关系。通过分子对接研究证实了大多数活性化合物与酶的关键结合相互作用。
