Design, modification, and bio-evaluation of salazinic acid derivatives

Data on synthesized derivatives of salazinic acid are scarce, with existing reports addressing only derivative hexaacetyl salazinic acid. This study investigated a set of novel potential antidiabetic agents. Analogs of salazinic acid were designed and synthesized using bromination, nucleophilic addi...

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Autores principales:	Nguyen-Kim-Tuyen Pham, Nguyen-Minh-An Tran, Huy Truong Nguyen, Duc-Dung Pham, Thi-Quynh-Trang Nguyen, Thi-Hong-Anh Nguyen, Huu-Tri Nguyen, Thanh-Hung Do, Ngoc-Hong Nguyen, Thuc-Huy Duong
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Lichen Bromination Nucleophilic addition α-glucosidase inhibition Molecular docking Kinetic Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/fb74b27e54f54a419bbf36b29bbda4e8
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spelling	oai:doaj.org-article:fb74b27e54f54a419bbf36b29bbda4e82021-11-26T04:26:07ZDesign, modification, and bio-evaluation of salazinic acid derivatives1878-535210.1016/j.arabjc.2021.103535https://doaj.org/article/fb74b27e54f54a419bbf36b29bbda4e82022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1878535221005505https://doaj.org/toc/1878-5352Data on synthesized derivatives of salazinic acid are scarce, with existing reports addressing only derivative hexaacetyl salazinic acid. This study investigated a set of novel potential antidiabetic agents. Analogs of salazinic acid were designed and synthesized using bromination, nucleophilic addition, Friedel-Crafts alkylation, and esterification. Ten synthetic compounds were prepared and structurally elucidated, including eight new compounds (1a-1c, 2a, 3a, 3b, 4a, 4b) and two known analogs. Under bromination, salazinic acid (1) enabled the following reaction chain: oxidation, decarboxylation, and substitution. This yielded products 1a-1c, which were found to have unprecedented scaffolds. Parmosidone F (5) was prepared from 1 with orsellinic acid via Friedel-Crafts alkylation, confirming a previously reported biosynthesis route. These analogs were evaluated for enzyme inhibition of α-glucosidase, and all showed more potent activity than that of acarbose, a positive control (IC50 332 μM), with IC50 values in the range 9.32–39.96 μM. An in silico molecular docking model confirmed that, in terms of enzyme inhibition, the compounds ranked as follows: 3b > 4b > 4a > 1c > 2a > 1b > 1a > 3a. The kinetics of enzyme inhibition showed 4a and 5 to be a non-competitive-type and mixed-type inhibitors, respectively.Nguyen-Kim-Tuyen PhamNguyen-Minh-An TranHuy Truong NguyenDuc-Dung PhamThi-Quynh-Trang NguyenThi-Hong-Anh NguyenHuu-Tri NguyenThanh-Hung DoNgoc-Hong NguyenThuc-Huy DuongElsevierarticleLichenBrominationNucleophilic additionα-glucosidase inhibitionMolecular dockingKineticChemistryQD1-999ENArabian Journal of Chemistry, Vol 15, Iss 1, Pp 103535- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Lichen Bromination Nucleophilic addition α-glucosidase inhibition Molecular docking Kinetic Chemistry QD1-999
spellingShingle	Lichen Bromination Nucleophilic addition α-glucosidase inhibition Molecular docking Kinetic Chemistry QD1-999 Nguyen-Kim-Tuyen Pham Nguyen-Minh-An Tran Huy Truong Nguyen Duc-Dung Pham Thi-Quynh-Trang Nguyen Thi-Hong-Anh Nguyen Huu-Tri Nguyen Thanh-Hung Do Ngoc-Hong Nguyen Thuc-Huy Duong Design, modification, and bio-evaluation of salazinic acid derivatives
description	Data on synthesized derivatives of salazinic acid are scarce, with existing reports addressing only derivative hexaacetyl salazinic acid. This study investigated a set of novel potential antidiabetic agents. Analogs of salazinic acid were designed and synthesized using bromination, nucleophilic addition, Friedel-Crafts alkylation, and esterification. Ten synthetic compounds were prepared and structurally elucidated, including eight new compounds (1a-1c, 2a, 3a, 3b, 4a, 4b) and two known analogs. Under bromination, salazinic acid (1) enabled the following reaction chain: oxidation, decarboxylation, and substitution. This yielded products 1a-1c, which were found to have unprecedented scaffolds. Parmosidone F (5) was prepared from 1 with orsellinic acid via Friedel-Crafts alkylation, confirming a previously reported biosynthesis route. These analogs were evaluated for enzyme inhibition of α-glucosidase, and all showed more potent activity than that of acarbose, a positive control (IC50 332 μM), with IC50 values in the range 9.32–39.96 μM. An in silico molecular docking model confirmed that, in terms of enzyme inhibition, the compounds ranked as follows: 3b > 4b > 4a > 1c > 2a > 1b > 1a > 3a. The kinetics of enzyme inhibition showed 4a and 5 to be a non-competitive-type and mixed-type inhibitors, respectively.
format	article
author	Nguyen-Kim-Tuyen Pham Nguyen-Minh-An Tran Huy Truong Nguyen Duc-Dung Pham Thi-Quynh-Trang Nguyen Thi-Hong-Anh Nguyen Huu-Tri Nguyen Thanh-Hung Do Ngoc-Hong Nguyen Thuc-Huy Duong
author_facet	Nguyen-Kim-Tuyen Pham Nguyen-Minh-An Tran Huy Truong Nguyen Duc-Dung Pham Thi-Quynh-Trang Nguyen Thi-Hong-Anh Nguyen Huu-Tri Nguyen Thanh-Hung Do Ngoc-Hong Nguyen Thuc-Huy Duong
author_sort	Nguyen-Kim-Tuyen Pham
title	Design, modification, and bio-evaluation of salazinic acid derivatives
title_short	Design, modification, and bio-evaluation of salazinic acid derivatives
title_full	Design, modification, and bio-evaluation of salazinic acid derivatives
title_fullStr	Design, modification, and bio-evaluation of salazinic acid derivatives
title_full_unstemmed	Design, modification, and bio-evaluation of salazinic acid derivatives
title_sort	design, modification, and bio-evaluation of salazinic acid derivatives
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/fb74b27e54f54a419bbf36b29bbda4e8
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Design, modification, and bio-evaluation of salazinic acid derivatives

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