IDENTIFICATION OF FLAVONOIDS FROM ACALYPHA INDICA L. (EUPHORBIACEAE) AS CASPASE-3 ACTIVATORS USING MOLECULAR DOCKING AND MOLECULAR DYNAMICS

ELLIN FEBRINA; AIYI ASNAWI; RIZKY ABDULAH; KERI LESTARI; UNANG SUPRATMAN

doi:10.22159/ijap.2022.v14s5.34

Authors

ELLIN FEBRINA Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km. 21, Jatinangor, 45363, Indonesia
AIYI ASNAWI Department of Pharmacochemistry, Faculty of Pharmacy, Universitas Bhakti Kencana, Jl. Soekarno-Hatta No. 754, Bandung, 40617, Indonesia
RIZKY ABDULAH Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km. 21, Jatinangor, 45363, Indonesia
KERI LESTARI Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km. 21, Jatinangor, 45363, Indonesia, Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km. 21, Jatinangor, 45363, Indonesia
UNANG SUPRATMAN Department of Chemistry, Faculty of Mathematics and Natural Sciences, Central Laboratory, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km. 21, Jatinangor, 45363, Indonesia

DOI:

https://doi.org/10.22159/ijap.2022.v14s5.34

Keywords:

Acalypha indica L., Caspase-3, Molecular docking, Molecular dynamics

Abstract

Objective: The purpose of this study was to determine the structural-based molecular interactions between flavonoids contained in Acalypha indica L. and caspase-3 by molecular docking and molecular dynamics (MD) simulations.

Methods: In a computer simulation, ten flavonoids contained in A. indica L. were evaluated for caspase-3 using the X-ray crystal structure of human caspase-3 (PDB ID 1NME). The AutoDock 4.2 software was used to study molecular docking, and MD simulations were done with GROMACS v2018.

Results: The results of molecular docking identified the top four compounds, namely nicotiflorin, naringenin, hesperetin, and kaempferol, with docking scores of-6.81,-6.45,-6.33, and-6.10 kcal/mol, respectively. According to the MD simulation results, nicotiflorin was most effective in stabilizing the complex with caspase-3, with a total energy (ΔG_bind, MM-PBSA) of-96.315 kcal/mol.

Conclusion: This study showed that nicotiflorin was the flavonoid in A. indica L. that activated caspase-3 the best.

Downloads

Download data is not yet available.

References

Yadav P, Yadav R, Jain S, Vaidya A. Caspase-3: A primary target for natural and synthetic compounds for cancer therapy. Chem Biol Drug Des. 2021;98(1):144-65. doi: 10.1111/cbdd.13860, PMID 33963665.

Vaidya A, Jain AK, Prashantha Kumar BR, Sastry GN, Kashaw SK, Agrawal RK. CoMFA, CoMSIA, kNN MFA and docking studies of 1,2,4-oxadiazole derivatives as potent caspase-3 activators. Arab J Chem. 2017 May 1;10:S3936-46. doi: 10.1016/j.arabjc.2014.05.034.

Winter R, Kramer A, Borkowski A, Research NK-C. Undefined loss of caspase-1 and caspase-3 protein expression in human prostate cancer. American Association for Cancer Research. 2001. Available from: https://aacrjournals.org/cancerres/article-abstract/61/3/1227/508256. [Last accessed on 15 Nov 2022]

Zahidin NS, Saidin S, Zulkifli RM, Muhamad II, Ya’akob H, Nur H. A review of Acalypha indica L. (Euphorbiaceae) as a traditional medicinal plant and its therapeutic potential. J Ethnopharmacol. 2017 Jul 31;207:146-73. doi: 10.1016/j.jep.2017.06.019, PMID 28647509.

Kumar K, Chetty C. In vitro anthelmintic activity of roots of Acalypha indica Linn. controlled drug delivery view project formulation and characterization of ofloxacin microspheres prepared by ionotropic gelation technique view project alagusundaram muthumanickam ratnam ins. Artic Int J PharmTech Res. 2009;1(4):1499-502.

Maleki SJ, Crespo JF, Cabanillas B. Anti-inflammatory effects of flavonoids. Food Chem. 2019 Nov;299:125124. doi: 10.1016/j.foodchem.2019.125124, PMID 31288163.

Juca MM, Cysne Filho FMS, de Almeida JC, Mesquita DDS, Barriga JRM, Dias KCF. Flavonoids: biological activities and therapeutic potential. Nat Prod Res. 2020 Mar 3;34(5):692-705. doi: 10.1080/14786419.2018.1493588, PMID 30445839.

Panche AN, Diwan AD, Chandra SR. Flavonoids: an overview. J Nutr Sci. 2016 Dec 29;5:e47. doi: 10.1017/jns.2016.41, PMID 28620474.

George VC, Dellaire G, Rupasinghe HPV. Plant flavonoids in cancer chemoprevention: role in genome stability. J Nutr Biochem. 2017 Jul 1;45:1-14. doi: 10.1016/j.jnutbio.2016.11.007, PMID 27951449.

Srivastava S, Somasagara RR, Hegde M, Nishana M, Tadi SK, Srivastava M. Quercetin, a natural flavonoid interacts with DNA, arrests cell cycle and causes tumor regression by activating mitochondrial pathway of apoptosis. Sci Rep. 2016 Apr 12;6:24049. doi: 10.1038/srep24049, PMID 27068577.

Sabe VT, Ntombela T, Jhamba LA, Maguire GEMM, Govender T, Naicker T. Current trends in computer-aided drug design and a highlight of drugs discovered via computational techniques: a review. Eur J Med Chem. 2021 Nov 15;224:113705. doi: 10.1016/j.ejmech.2021.113705, PMID 34303871.

Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS. AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem. 2009 Dec 1;30(16):2785-91. doi: 10.1002/jcc.21256. PMID 19399780.

Erlanson DA, Lam JW, Wiesmann C, Luong TN, Simmons RL, DeLano WL. In situ assembly of enzyme inhibitors using extended tethering. Nat Biotechnol. 2003 Mar 1;21(3):308-14. doi: 10.1038/nbt786, PMID 12563278.

Febrina E, Alamhari RK, Abdulah R, Lestari K, Levita J, Supratman U. Molecular docking and molecular dynamics studies of Acalypha Indica L. phytochemical constituents with caspase-3. Int J App Pharm. 2021 Dec 11;13Special Issue 4:210-5. doi: 10.22159/ijap.2021.v13s4.43861.

Kohnke B, Kutzner C, Grubmuller H. A GPU-accelerated fast multipole method for GROMACS: performance and accuracy. J Chem Theory Comput. 2020 Nov 10;16(11):6938-49. doi: 10.1021/acs.jctc.0c00744, PMID 33084336.

Kumari R, Kumar R, Open Source Drug Discovery Consortium, Lynn A. g_mmpbsa–a GROMACS tool for high-throughput MM-PBSA calculations. J Chem Inf Model. 2014 Jul;54(7):1951-62. doi: 10.1021/ci500020m, PMID 24850022.

Valdes Tresanco MS, Valdes Tresanco MES, Valiente PA, Moreno E. Gmx_MMPBSA: A new tool to perform end-state free energy calculations with GROMACS. J Chem Theory Comput. 2021 Oct 12;17(10):6281-91. doi: 10.1021/acs.jctc.1c00645, PMID 34586825.