Synthesis, α-glucosidase inhibition, and molecular docking studies of novel N-substituted hydrazide derivatives of atranorin as antidiabetic agents

Bioorg Med Chem Lett. 2020 Sep 1;30(17):127359. doi: 10.1016/j.bmcl.2020.127359.

Thuc-Huy Duong ¹, Asshaima Paramita Devi ², Nguyen-Minh-An Tran ³, Hoang-Vinh-Truong Phan ⁴, Ngoc-Vinh Huynh ⁵, Jirapast Sichaem ⁶, Hoai-Duc Tran ³, Mahboob Alam ⁷, Thi-Phuong Nguyen ⁸, Huu-Hung Nguyen ⁹, Warinthorn Chavasiri ², Tien-Cong Nguyen ¹⁰

Affiliations

1 Department for Management of Science and Technology Development, Ton Duc Thang University, Ho Chi Minh City, Viet Nam; Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Viet Nam. Electronic address: [email protected].
2 Center of Excellence in Natural Products Chemistry, Department of Chemistry, Faculty of Science, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand.
3 Industrial University of Ho Chi Minh, Ho Chi Minh City, Viet Nam.
4 Department of Chemistry, Ho Chi Minh City University of Education, 280 An Duong Vuong Street, District 5, 748342 Ho Chi Minh City, Viet Nam.
5 Department of Organic Chemistry, VNUHCM - University of Science, Ho Chi Minh City, Viet Nam.
6 Research Unit in Natural Products Chemistry and Bioactivities, Faculty of Science and Technology, Thammasat University Lampang Campus, Lampang 52190, Thailand. Electronic address: [email protected].
7 Division of Chemistry and Biotechnology, Dongguk University, 123 Dongdae-ro, Gyeongju 780-714, Republic of Korea.
8 NTT Hi-Tech Institute, Nguyen Tat Thanh University, 300A Nguyen Tat Thanh, District 4, Ho Chi Minh City, Viet Nam.
9 Faculty of Technology, Van Lang University, 45 Nguyen Khac Nhu, District 1, Ho Chi Minh City, Viet Nam.
10 Department of Chemistry, Ho Chi Minh City University of Education, 280 An Duong Vuong Street, District 5, 748342 Ho Chi Minh City, Viet Nam. Electronic address: [email protected].

PMID: 32738998 DOI: 10.1016/j.bmcl.2020.127359

Abstract

A series of novel N-substituted hydrazide derivatives were synthesized by reacting atranorin, a compound with a natural depside structure (1), with a range of hydrazines. The natural product and 12 new analogues (2-13) were investigated for inhibition of α-glucosidase. The N-substituted hydrazide derivatives showed more potent inhibition than the original. The experimental results were confirmed by docking analysis. This study suggests that these compounds are promising molecules for diabetes therapy. Molecular dynamics simulations were carried out with compound 2 demonstrating the best docking model using Gromac during simulation up to 20 ns to explore the stability of the complex ligand-protein. Furthermore, the activity of all synthetic compounds 2-13 against a normal cell line HEK293, used for assessing their cytotoxicity, was evaluated.

Keywords

Atranorin; Cytotoxicity; N-substituted hydrazide derivatives; Parmotrema tsavoense; α-Glucosidase inhibition.

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