Synthesis, α-glucosidase inhibition, α-amylase inhibition, and molecular docking studies of 3,3-di(indolyl)indolin-2-ones

Mardi Santoso; Li Lin Ong; Nur Pasca Aijijiyah; First Ambar Wati; Azminah Azminah; Rose Malina Annuur; Arif Fadlan; Zaher M A Judeh

doi:10.1016/j.heliyon.2022.e09045

Synthesis, α-glucosidase inhibition, α-amylase inhibition, and molecular docking studies of 3,3-di(indolyl)indolin-2-ones

Heliyon. 2022 Mar 4;8(3):e09045. doi: 10.1016/j.heliyon.2022.e09045. eCollection 2022 Mar.

Authors

Mardi Santoso¹, Li Lin Ong^{2

3}, Nur Pasca Aijijiyah¹, First Ambar Wati¹, Azminah Azminah⁴, Rose Malina Annuur¹, Arif Fadlan¹, Zaher M A Judeh^{3

5}

Affiliations

¹ Department of Chemistry, Faculty of Science, Institut Teknologi Sepuluh Nopember, Sukolilo, Surabaya, 60111, Indonesia.
² NTU Institute for Health Technologies, Interdisciplinary Graduate School, Nanyang Technological University, Research Techno Plaza, XFrontiers Block, #02-07, 50 Nanyang Drive, 637553, Singapore.
³ School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, N1.2-B1-14, 637459, Singapore.
⁴ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Surabaya, Surabaya, 60284, Indonesia.
⁵ Division of Chemistry & Biological Chemistry, School of Physical & Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637371, Singapore.

Abstract

The synthesized 3,3-di(indolyl)indolin-2-ones 1a-p showed desired higher α-glucosidase inhibitory activities and lower α-amylase inhibitory activities than standard drug acarbose. Particularly, compound 1i showed favorable higher α-glucosidase % inhibition of 67 ± 13 and lower α-amylase % inhibition of 51 ± 4 in comparison to acarbose with % inhibition activities of 19 ± 5 and 90 ± 2, respectively. Docking studies of selected 3,3-di(indolyl)indolin-2-ones revealed key interactions with the active sites of both α-glucosidase and α-amylase, further supporting the observed % inhibitory activities. Furthermore, the binding energies are consistent with the % inhibition values. The results suggest that 3,3-di(indolyl)indolin-2-ones may be developed as suitable Alpha Glucosidase Inhibitors (AGIs) and the lower α-amylase activities should be advantageous to reduce the side effects exhibited by commercial AGIs.

Keywords: 3,3-Di(indolyl)indolin-2-ones; Diabetes; Docking studies; α-amylase inhibition; α-glucosidase inhibition.