Rhodanine-benzamides as potential hits for α-amylase enzyme inhibitors and radical (DPPH and ABTS) scavengers

• Published in: Molecular diversity 2024-03
• Main Authors: Egu, Samuel Attah, Ali, Irfan, Khan, Khalid Mohammed, Chigurupati, Sridevi, Qureshi, Urooj, Salar, Uzma, Ul-Haq, Zaheer, Almahmoud, Suliman A, Felemban, Shatha Ghazi, Ali, Mohsin, Taha, Muhammad
• Format: Article
• Language: English
• ISSN: 1381-1991; 1573-501X
• DOI: 10.1007/s11030-024-10813-z

A series of 3-substituted and 3,5-disubstituted rhodanine-based derivatives were synthesized from 3-aminorhodanine and examined for α-amylase inhibitory, DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activities in vitro. These derivatives displayed significant α-amylase inhibitory potential with IC values of 11.01-56.04 µM in comparison to standard acarbose (IC  = 9.08 ± 0.07 µM). Especially, compounds 7 (IC  = 11.01 ± 0.07 µM) and 8 (IC  = 12.01 ± 0.07 µM) showed highest α-amylase inhibitory activities among the whole series. In addition to α-amylase inhibitory activity, all compounds also demonstrated significant scavenging activities against DPPH and ABTS radicals, with IC values ranging from 12.24 to 57.33 and 13.29-59.09 µM, respectively, as compared to the standard ascorbic acid (IC  = 15.08 ± 0.03 µM for DPPH; IC  = 16.09 ± 0.17 µM for ABTS). These findings reveal that the nature and position of the substituents on the phenyl ring(s) are crucial for variation in the activities. The structure-activity relationship (SAR) revealed that the compounds bearing an electron-withdrawing group (EWG) at para substitution possessed the highest activity. In kinetic studies, only the km value was changed, with no observed changes in Vmax, indicating a competitive inhibition. Molecular docking studies revealed important interactions between compounds and the α-amylase active pocket. Further advanced research needs to perform on the identified compounds in order to obtain potential antidiabetic agents.