AccScience Publishing / AN / Online First / DOI: 10.36922/AN025440109
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ORIGINAL RESEARCH ARTICLE

Aframomum melegueta (grains of paradise) compounds inhibit carbonic anhydrase XII in brain cancer: An in silico approach

Moses Orimoloye Akinjiyan1,2* ,  Titilayo Ibironke Ologunagba1 ,  Kolade Olatubosun Faloye3 ,  Oritoke Modupe Okeowo4 ,  Marvellous Damilola Akinola5 ,  Olusola Olalekan Elekofehinti2,6
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1 Department of Medical Biochemistry, School of Basic Medical Sciences, Federal University of Technology, Akure, Ondo State, Nigeria
2 Teady Bioscience Research Laboratory, Akure, Ondo State, Nigeria
3 Department of Industrial Chemistry, Faculty of Science, University of Ilesa, Ilesa, Osun State, Nigeria
4 Department of Physiology, School of Basic Medical Sciences, Federal University of Technology, Akure, Ondo State, Nigeria
5 Department of Biotechnology, School of Life Sciences, Federal University of Technology, Akure, Ondo State, Nigeria
6 Department of Biochemistry, School of Life Sciences, Federal University of Technology, Akure, Ondo State, Nigeria
Advanced Neurology, 025440109 https://doi.org/10.36922/AN025440109
Received: 2 November 2025 | Revised: 22 March 2026 | Accepted: 20 April 2026 | Published online: 19 May 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Carbonic anhydrase XII (CA) has emerged as a critical therapeutic target in brain cancer, particularly glioma, which is characterized by rapid proliferation, a highly invasive nature, and resistance to therapy. Aframomum melegueta (grains of paradise) is a medicinal plant whose bioactive compounds are reported to possess anticancer properties. This study investigates the inhibitory potentials of these phytocompounds on CA using an in silico approach. The molecular docking of 141 A. melegueta bioactive compounds, along with standard carbonic anhydrase inhibitors (SCAI; acetazolamide and SLC-0111), was performed using the Schrödinger suite. Induced-fit docking; molecular mechanics with generalized Born and surface area solvation (MMGBSA); absorption, distribution, metabolism, and excretion; and automated quantitative structure–activity relationship analyses of the hit compounds were performed. The binding affinity of 1-(3,4-dihydroxy-5-methoxyphenyl)-7-(3,4-dihydroxyphenyl)heptane-3,5-diyldiacetate (−10.230 kcal/mol) and 1,7-bis(3,4-dihydroxy-5-methoxyphenyl)heptane-3,5-diyldiacetate (−8.564 kcal/mol) with CA was better compared to acetazolamide (−5.225 kcal/mol) and SLC-0111 (−3.792 kcal/mol). Amino acids VAL 125, VAL 147, LEU 203, and TRP 214 play crucial roles in stabilizing the compounds. The induced-fit docking score of 1-(3,4-dihydroxy-5-methoxyphenyl)-7-(3,4-dihydroxyphenyl)heptane-3,5-diyldiacetate (−579.84 kcal/mol) and 1,7-bis(3,4-dihydroxy-5-methoxyphenyl)heptane-3,5-diyldiacetate (−576.49 kcal/mol) were better than the SCAIs. The MMGBSA analysis showed that the binding complexes of the hit compounds were stable, and their pharmacotoxicity profiles complied with Lipinski’s rule of druggability. The predicted pIC50 of 1-(3,4-dihydroxy-5-methoxyphenyl)-7-(3,4-dihydroxyphenyl)heptane-3,5-diyldiacetate (4.9607) was higher than that of acetazolamide (4.3003) and SLC-0111 (4.7022), suggesting greater potency at minimum concentration. Molecular dynamics simulation at 200 ns further validated the inhibitory potential of 1-(3,4-dihydroxy-5-methoxyphenyl)- 7-(3,4-dihydroxyphenyl)heptane-3,5-diyldiacetate (−10.230 kcal/mol) and 1,7-bis(3,4-dihydroxy-5-methoxyphenyl)heptane-3,5-diyldiacetate (−8.564 kcal/ mol). The findings suggest that these A. melegueta hit compounds are strong CA inhibitors and can be used to develop novel therapeutic agents for treating brain cancer.

Keywords
Aframomum melegueta
Carbonic anhydrase XII
Brain cancer
Molecular and induced-fit docking
Molecular dynamics simulation
Funding
None.
Conflict of interest
The authors declare no conflicts of interest.
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Advanced Neurology, Electronic ISSN: 2810-9619 Print ISSN: 3060-8589, Published by AccScience Publishing
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