Anti-α-Glucosidase, SAR Analysis, and Mechanism Investigation of Indolo[1,2-b]isoquinoline Derivatives

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2023 Jul 14

PMID 37446942

Authors

Mengyue Li

Lin Li

Li Lu

Xuetao Xu

Jinhui Hu

Jin-Bao Peng

Affiliations

Soon will be listed here.

Abstract

To find potential α-glucosidase inhibitors, indolo[1,2-b]isoquinoline derivatives (-) were screened for their α-glucosidase inhibitory effects. All derivatives presented potential α-glucosidase inhibitory effects with IC values of 3.44 ± 0.36~41.24 ± 0.26 μM compared to the positive control acarbose (IC value: 640.57 ± 5.13 μM). In particular, compound displayed the strongest anti-α-glucosidase activity, being ~186 times stronger than acarbose. Kinetic studies found that compounds , , , , and were all reversible mix-type inhibitors. The 3D fluorescence spectra and CD spectra results revealed that the interaction between compounds , , , , and and α-glucosidase changed the conformational changes of α-glucosidase. Molecular docking and molecular dynamics simulation results indicated the interaction between compounds and α-glucosidase. In addition, cell cytotoxicity and drug-like properties of compound were also investigated.

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References

Acar Cevik U, Celik I, Pasayeva L, Fatullayev H, Bostanci H, Ozkay Y . New benzimidazole-oxadiazole derivatives: Synthesis, α-glucosidase, α-amylase activity, and molecular modeling studies as potential antidiabetic agents. Arch Pharm (Weinheim). 2023; 356(5):e2200663. DOI: 10.1002/ardp.202200663. View

Hu C, Wang W, Ye Y, Kang Y, Lin J, Wu P . Novel cinnamic acid magnolol derivatives as potent α-glucosidase and α-amylase inhibitors: Synthesis, in vitro and in silico studies. Bioorg Chem. 2021; 116:105291. DOI: 10.1016/j.bioorg.2021.105291. View

Li L, Liu X, Qi Z, Yang A, Ma A, Peng J . Palladium-Catalyzed Carbonylative Sonogashira/Annulation Reaction: Synthesis of Indolo[1,2-]isoquinolines. Org Lett. 2022; 24(5):1201-1206. DOI: 10.1021/acs.orglett.1c04350. View

Mushtaq A, Azam U, Mehreen S, Naseer M . Synthetic α-glucosidase inhibitors as promising anti-diabetic agents: Recent developments and future challenges. Eur J Med Chem. 2023; 249:115119. DOI: 10.1016/j.ejmech.2023.115119. View

Xu X, Deng X, Chen J, Liang Q, Zhang K, Li D . Synthesis and biological evaluation of coumarin derivatives as α-glucosidase inhibitors. Eur J Med Chem. 2020; 189:112013. DOI: 10.1016/j.ejmech.2019.112013. View

Tan K, Tesar C, Wilton R, Jedrzejczak R, Joachimiak A . Interaction of antidiabetic α-glucosidase inhibitors and gut bacteria α-glucosidase. Protein Sci. 2018; 27(8):1498-1508. PMC: 6153411. DOI: 10.1002/pro.3444. View

Zheng P, Xiong Z, Liao C, Zhang X, Feng M, Wu X . and studies of bis (indol-3-yl) methane derivatives as potential α-glucosidase and α-amylase inhibitors. J Enzyme Inhib Med Chem. 2021; 36(1):1938-1951. PMC: 8409970. DOI: 10.1080/14756366.2021.1971976. View

Wang Y, Zheng T, Huo Y, Du W . Exploration of Isoquinoline Alkaloids as Potential Inhibitors against Human Islet Amyloid Polypeptide. ACS Chem Neurosci. 2022; 13(14):2164-2175. DOI: 10.1021/acschemneuro.2c00206. View

Fattaheian-Dehkordi S, Hojjatifard R, Saeedi M, Khanavi M . A Review on Antidiabetic Activity of spp.: A New Approach for Developing Herbal Remedies. Evid Based Complement Alternat Med. 2021; 2021:5587938. PMC: 8275385. DOI: 10.1155/2021/5587938. View

10.

Adler A, Bennett P, Colagiuri Chair S, Gregg E, Narayan K, Schmidt M . REPRINT OF: CLASSIFICATION OF DIABETES MELLITUS. Diabetes Res Clin Pract. 2021; :108972. DOI: 10.1016/j.diabres.2021.108972. View

11.

Kerru N, Singh-Pillay A, Awolade P, Singh P . Current anti-diabetic agents and their molecular targets: A review. Eur J Med Chem. 2018; 152:436-488. DOI: 10.1016/j.ejmech.2018.04.061. View

12.

Wongon M, Limpeanchob N . Inhibitory effect of Roxb and oxyresveratrol on α-glucosidase and sugar digestion in Caco-2 cells. Heliyon. 2020; 6(3):e03458. PMC: 7056649. DOI: 10.1016/j.heliyon.2020.e03458. View

13.

Ozil M, Parlak C, Baltas N . A simple and efficient synthesis of benzimidazoles containing piperazine or morpholine skeleton at C-6 position as glucosidase inhibitors with antioxidant activity. Bioorg Chem. 2017; 76:468-477. DOI: 10.1016/j.bioorg.2017.12.019. View

14.

Serra-Barcellona C, Habib N, Honore S, Sanchez S, Genta S . Enhydrin Regulates Postprandial Hyperglycemia in Diabetic Rats by Inhibition of α-Glucosidase Activity. Plant Foods Hum Nutr. 2017; 72(2):156-160. DOI: 10.1007/s11130-017-0600-y. View

15.

Hameed S, Kanwal , Seraj F, Rafique R, Chigurupati S, Wadood A . Synthesis of benzotriazoles derivatives and their dual potential as α-amylase and α-glucosidase inhibitors in vitro: Structure-activity relationship, molecular docking, and kinetic studies. Eur J Med Chem. 2019; 183:111677. DOI: 10.1016/j.ejmech.2019.111677. View

16.

Khan I, Khan A, Ahsan Halim S, Khan M, Zaib S, Al-Yahyaei B . Utilization of the common functional groups in bioactive molecules: Exploring dual inhibitory potential and computational analysis of keto esters against α-glucosidase and carbonic anhydrase-II enzymes. Int J Biol Macromol. 2020; 167:233-244. DOI: 10.1016/j.ijbiomac.2020.11.170. View

17.

Fan M, Yang W, Peng Z, He Y, Wang G . Chromone-based benzohydrazide derivatives as potential α-glucosidase inhibitor: Synthesis, biological evaluation and molecular docking study. Bioorg Chem. 2022; 131:106276. DOI: 10.1016/j.bioorg.2022.106276. View

18.

Moghadam Farid S, Noori M, Nazari Montazer M, Khalili Ghomi M, Mollazadeh M, Dastyafteh N . Synthesis and structure-activity relationship studies of benzimidazole-thioquinoline derivatives as α-glucosidase inhibitors. Sci Rep. 2023; 13(1):4392. PMC: 10020548. DOI: 10.1038/s41598-023-31080-2. View

19.

Pogaku V, Gangarapu K, Basavoju S, Tatapudi K, Katragadda S . Design, synthesis, molecular modelling, ADME prediction and anti-hyperglycemic evaluation of new pyrazole-triazolopyrimidine hybrids as potent α-glucosidase inhibitors. Bioorg Chem. 2019; 93:103307. DOI: 10.1016/j.bioorg.2019.103307. View

20.

Lam D, LeRoith D . The worldwide diabetes epidemic. Curr Opin Endocrinol Diabetes Obes. 2012; 19(2):93-6. DOI: 10.1097/MED.0b013e328350583a. View