KMID : 0545120200300040552
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Journal of Microbiology and Biotechnology 2020 Volume.30 No. 4 p.552 ~ p.560
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Two flavonoid-based compounds from Murraya paniculata as novel human carbonic anhydrase isozyme II inhibitors detected by a resazurin yeast-based assay
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Sangkaew Anyaporn
Samritsakulchai Nawara Sanachai Kamonpan Rungrotmongkol Thanyada Chavasiri Warinthorn Yompakdee Chulee
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Abstract
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Human carbonic anhydrase isozyme II has been used as protein target for disorder treatment including glaucoma. Current clinically used sulfonamide-based CA inhibitors can induce side effects, and so alternatives are required. This study aimed to investigate a natural CA inhibitor from Murraya paniculata. The previously developed yeast-based assay was used to screen 14 compounds isolated from M. paniculata and identified by NMR analysis for anti-human CA isozyme II (hCAII) activity. Cytotoxicity of the compounds was also tested using the same yeast-based assay but in a different cultivation condition. Two flavonoid candidate compounds, 5, 6, 7, 8, 3?, 4?, 5?-heptamethoxyflavone (4) and 3 ,5, 7, 8, 3?, 4?, 5?-heptamethoxyflavone (9), showed potent inhibitory activity against hCAII with a minimal effective concentration of 10.8 and 21.5 ¥ìM, respectively, while they both exhibited no cytotoxic effect even at the highest concentration tested (170 ¥ìM). The results from an in vitro esterase assay of the two candidates confirmed their hCAII inhibitory activity with IC50 values of 24.0 and 34.3 ¥ìM, respectively. To investigate the potential inhibition mechanism of compound 4, in silico molecular docking was performed using the FlexX and Swissdock software. This revealed that compound 4 coordinated with the Zn2+ ion in the hCAII active site through its methoxy oxygen at a distance of 1.60 A (FlexX) or 2.29 A (Swissdock). The interaction energy of compound 4 with hCAII was -13.36 kcal/mol. Thus, compound 4 is a potent novel flavonoid-based hCAII inhibitor and may be useful for further anti-CAII design and development.
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KEYWORD
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Human carbonic anhydrase isozyme II (hCAII), carbonic anhydrase inhibitor, glaucoma, murraya paniculata, yeast-based assay, flavonoid
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