Umoh Esther Udo,
Dibua Redeemed Ihimoya,
Buraimoh Bose Olaide,
- Researcher Department of Biochemistry, Federal University Akure Nigeria
- Researcher Department of Biochemistry, Federal University Akure Nigeria
- Researcher Department of Biochemistry, Federal University Akure Nigeria
Abstract
Computational mimicry of structure of large complexes created by di and poly interaction of molecule has been termed molecular docking. The purpose of molecular docking is in prediction of the three dimensional structures of interest, this is due that Docking only produces plausible candidate structures. The docking was carried out between the bioactive compounds against 5α-reductase, 3β-hydroxy-steroid dehydrogenase and 17β-hydroxy-steroid dehydrogenase of returned a binding energy, BE (kcal/mol) between -5.9 and -9.0 kcal/mol; -6.0 and -9.4 kcal/mol; and -5.2 kcal/mol and -8.0 kcal/mol respectively tables Apigenin and ellagic acid were the compounds with least binding energy, which translate to high binding affinity to three protein targets. This might be one of the mechanism in which Aframomum melegueta play its anti-cancer role in the disease by binding of the compounds identified in it to the active site of 5α-reductase, 3β-hydroxy-steroid dehydrogenase and 17β-hydroxy-steroid dehydrogenase enzymes. Aframomum melegueta has bioactive chemicals that may inhibit three important enzymes involved in human steroid metabolism: 5α-reductase, 3β-hydroxy-steroid dehydrogenase, and 17β-hydroxy-steroid dehydrogenase. This study looked into the potential of these compounds to inhibit these enzymes. The findings of molecular docking tests showed that the binding energies for the different targets ranged from -5.9 to -9.0 kcal/mol, -6.0 to -9.4 kcal/mol, and -5.2 to -8.0 kcal/mol. Interestingly, the lowest binding energies were found for apigenin and ellagic acid, indicating a high binding affinity to all three protein targets. The involvement of hydrogen bonds and hydrophobic interactions between the bioactive chemicals and amino acid residues at the enzyme binding sites was demonstrated by molecular interaction analysis. These results shed light on the possible mechanism by which chemicals from Aframomum melegueta may impede these enzymes that metabolize steroids to produce anti-cancer effects.
Keywords: Molecular docking, Bioactive component, Aframomum melegueta, Protein ligand interaction
References
- Ajaiyeoba EO, Ekundayo O. Essential oil constituents of Aframomum melegueta (Roscoe) K. Schum. seeds (alligator pepper) from Nigeria. Flavour and fragrance journal. 1999 Mar;14(2):109-11.
- Begley DW, Edwards TE, Raymond AC, Smith ER, Hartley RC, Abendroth J, Sankaran B, Lorimer DD, Myler PJ, Staker BL, Stewart LJ. Inhibitor-bound complexes of dihydrofolate reductase-thymidylate synthase from Babesia bovis. Acta Crystallographica Section F: Structural Biology and Crystallization Communications. 2011 Sep 1;67(9):1070-7.
- Thomas JL, Mack VL, Glow JA, Moshkelani D, Terrell JR, Bucholtz KM. Structure/function of the inhibition of human 3β-hydroxysteroid dehydrogenase type 1 and type 2 by trilostane. The Journal of steroid biochemistry and molecular biology. 2008 Jul 1;111(1-2):66-73.
- Dallakyan S, Olson AJ. Small-molecule library screening by docking with PyRx. Chemical biology: methods and protocols. 2015:243-50.
- Inegbenebor U, Ebomoyi MI, Onyia KA, Amadi K, Aigbiremolen AE. Effect of aqueous extract of alligator pepper (Zingiberaceae Aframomum melegueta) on gestational weight gain. Nigerian journal of physiological sciences. 2009;24(2).
- Boon NA, Colledge NR, Walker BR, Hunter JA, Davidson LS. Davidson’s principles and practice of medicine. (No Title). 2006 Jun 1.
- Kitchen DB, Decornez H, Furr JR, Bajorath J. Docking and scoring in virtual screening for drug discovery: methods and applications. Nature reviews Drug discovery. 2004 Nov;3(11):935-49.
- Bashir F, Komal A, Ibrahim A, Ain QT, Rehman B, Zaheer T. Exploring Nature’s Invigorating Power: Phytotherapy for SARS-CoV-2. Phytopharmacological Communications. 2023 Jun 30;3(01):39-51.
- Li T, Stephen P, Zhu DW, Shi R, Lin SX. Crystal structures of human 17β‐hydroxysteroid dehydrogenase type 1 complexed with estrone and NADP+ reveal the mechanism of substrate inhibition. The FEBS journal. 2019 Jun;286(11):2155-66.
- Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE. UCSF Chimera—a visualization system for exploratory research and analysis. Journal of computational chemistry. 2004 Oct;25(13):1605-12.
- Moret ES. Trans-atlantic diaspora ethnobotany: legacies of west African and iberian mediterranean migration in central Cuba. African Ethnobotany in the Americas. 2013:217-45.
- Seeliger D, de Groot BL. Ligand docking and binding site analysis with PyMOL and Autodock/Vina. Journal of computer-aided molecular design. 2010 May;24(5):417-22.
- Schulz V, VE T. A Physician’s Guide to Herbal Medicine. Rational Phytotherapy, 4th ed., Berlin: Springer‑Verlag. 2001.
- O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of computational chemistry. 2010 Jan 30;31(2):455-61.
- Umar HI, Ajayi A, Bello RO, Alabere HO, Sanusi AA, Awolaja OO, Alshehri MM, Chukwuemeka PO. Novel molecules derived from 3-O-(6-galloylglucoside) inhibit main protease of SARS-CoV 2 in silico. Chemical Papers. 2022 Feb 1:1-2.
- Xiao Q, Wang L, Supekar S, Shen T, Liu H, Ye F, Huang J, Fan H, Wei Z, Zhang C. Structure of human steroid 5α-reductase 2 with the anti-androgen drug finasteride. Nature Communications. 2020 Oct 27;11(1):5430.
| Volume | |
| Received | December 30, 2023 |
| Accepted | May 10, 2024 |
| Published | August 9, 2024 |