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Current Cancer Therapy Reviews

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ISSN (Print): 1573-3947
ISSN (Online): 1875-6301

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Research Article

Identification of Potential Lead Compounds against BCL-2 through In-silico Screening of Phytochemicals of Nigella sativa and Cuscuta reflexa for Oral Squamous Cell Carcinoma Management

Author(s): Fazulunisa Begum N., Pratibha Ramani, Mukesh Doble and Abilasha Ramasubramanian*

Volume 20, Issue 4, 2024

Published on: 10 October, 2023

Page: [410 - 416] Pages: 7

DOI: 10.2174/0115733947249560231003111214

Price: $65

Abstract

Significance of the Study: In silico analysis is frequently used in physicochemical characterisation, the discovery and improvement of novel compounds with affinity to a target, and the elucidation of absorption, distribution, metabolism, excretion, and toxicity features.

Aim and Objective: The aim of this study is to assess the efficacy of Nigella sativa and Cuscuta reflexa in targeting Bcl2-antiapoptotic protein in Oral Squamous Cell Carcinoma through in silico analysis.

Materials and Methods: The present study was designed to formulate a drug against Oral Squamous cell carcinoma against the target protein Bcl-2. Protein Database (PDB) was used to select and analyse the protein. Based on the literature search, the original molecules selected were thymoquinone, tannin pyrogallol, Cuscutin, kaempferol, nigellicine and the ligand structures were obtained ZINC15 database. Target protein structure was recognised through Protein sequence from PB (Protein Data Bank). Swiss ADME was used for assessing the properties of the molecules. Twenty new molecules were identified from zinc pharmer and docking was done for all the 20 using Swiss dock. Binding energy was assessed and compared with the original molecules.

Results: ZINC73690300 and ZINC73690304 had better binding energy than that of the original molecules. Both molecules can be potential candidates for Bcl-2 inhibition to prevent OSCC.

Conclusion: The present study evaluated the binding energy and bioavailability of the combined extract, thus attempting to predict the target ligand binding between the compounds in OSCC before attempting in vitro studies.

Keywords: Nigella sativa, Cuscuta reflexa, drug design, OSCC, ADME, Bcl-2 inhibition.

« Previous Next »
[1]
Vandenbulcke M, Dröes RM, Schokkaert E. Dementia and Society. Cambridge University Press 2022.https://books.google.com/books/about/Dementia_and_Society.html?hl=&id=VhlyEAAAQBAJ
[http://dx.doi.org/10.1017/9781108918954]
[2]
Hughes JP, Rees S, Kalindjian SB, Philpott KL. Principles of early drug discovery. Br J Pharmacol 2011; 162(6): 1239-49.
[http://dx.doi.org/10.1111/j.1476-5381.2010.01127.x] [PMID: 21091654]
[3]
Bentham Science Publisher BSP. Methods for the Prediction of Protein-Ligand Binding Sites for Structure-Based Drug Design and Virtual Ligand Screening. Curr Protein Pept Sci 2006; 7(5): 395-406.
[http://dx.doi.org/10.2174/138920306778559386]
[4]
Meng XY, Zhang HX, Mezei M, Cui M. Molecular docking: A powerful approach for structure-based drug discovery. Curr Computeraided Drug Des 2011; 7(2): 146-57.
[http://dx.doi.org/10.2174/157340911795677602] [PMID: 21534921]
[5]
Sterling T, Irwin JJ. ZINC 15 – Ligand Discovery for Everyone. J Chem Inf Model 2015; 55(11): 2324-37.
[http://dx.doi.org/10.1021/acs.jcim.5b00559] [PMID: 26479676]
[6]
Ahmad A, Husain A, Mujeeb M, et al. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac J Trop Biomed 2013; 3(5): 337-52.
[http://dx.doi.org/10.1016/S2221-1691(13)60075-1] [PMID: 23646296]
[7]
Ekins S, Mestres J, Testa B. In silico pharmacology for drug discovery: Methods for virtual ligand screening and profiling. Br J Pharmacol 2007; 152(1): 9-20.
[http://dx.doi.org/10.1038/sj.bjp.0707305] [PMID: 17549047]
[8]
Hannan MA, Rahman MA, Sohag AAM, et al. Black Cumin (Nigella sativa L.): A Comprehensive Review on Phytochemistry, Health Benefits, Molecular Pharmacology, and Safety. Nutrients 2021; 13(6): 1784.
[http://dx.doi.org/10.3390/nu13061784] [PMID: 34073784]
[9]
Kulyar MFA, Li R, Mehmood K, Waqas M, Li K, Li J. Potential influence of Nagella sativa (Black cumin) in reinforcing immune system: A hope to decelerate the COVID-19 pandemic. Phytomedicine 2021; 85: 153277.
[http://dx.doi.org/10.1016/j.phymed.2020.153277] [PMID: 32773257]
[10]
Rehman MU, Majid S. Therapeutic Applications of Honey and its Phytochemicals. Berlin: Springer Nature 2020; p. 1.
[11]
Shazia M, Imran K, Jasmine F, Mohd S, Huma M. Anti-bacterial, anti-oxidant and cytotoxicity of aqueous and organic extracts of Ricinus communis. Afr J Microbiol Res 2016; 10(8): 260-70.
[http://dx.doi.org/10.5897/AJMR2015.7397]
[12]
Ansari A, Viquar U, Kazmi MH. Aftimoon (Cuscuta reflexa Roxb): A parasitic plant with therapeutic potentials. Acta Sci Pharmaceut Sci 2020; 4: 90-7.
[http://dx.doi.org/10.31080/ASPS.2020.04.0622]
[13]
Maheswari TNU, Venugopal A, Sureshbabu N, Ramani P. Salivary micro RNA as a potential biomarker in oral potentially malignant disorders: A systematic review. Tzu-Chi Med J 2018; 30(2): 55-60.
[http://dx.doi.org/10.4103/tcmj.tcmj_114_17] [PMID: 29875583]
[14]
Youle RJ, Strasser A. The BCL-2 protein family: Opposing activities that mediate cell death. Nat Rev Mol Cell Biol 2008; 9(1): 47-59.
[http://dx.doi.org/10.1038/nrm2308] [PMID: 18097445]
[15]
Popović B, Jekić B, Novaković I, et al. Bcl-2 expression in oral squamous cell carcinoma. Ann N Y Acad Sci 2007; 1095(1): 19-25.
[http://dx.doi.org/10.1196/annals.1397.003] [PMID: 17404013]
[16]
Zhang M, Zhang P, Zhang C, et al. Prognostic significance of Bcl-2 and Bax protein expression in the patients with oral squamous cell carcinoma. J Oral Pathol Med 2009; 38(3): 307-13.
[http://dx.doi.org/10.1111/j.1600-0714.2008.00689.x] [PMID: 18710422]
[17]
Lo Muzio L, Mignogna M, Pannone G, et al. Expression of bcl-2 in oral squamous cell carcinoma: An immunohistochemical study of 90 cases with clinico-pathological correlations. Oncol Rep 2003; 10(2): 285-91.
[http://dx.doi.org/10.3892/or.10.2.285] [PMID: 12579259]
[18]
Escobar E, Gómez-Valenzuela F, Peñafiel C, Hormazábal-Hevia A, Herrera-Fuentes C, Mori-Aliaga D. Immunohistochemical expression of COX-2, Ki-67, Bcl-2, Bax, VEGF and CD105 according to histological grading in oral squamous cell carcinoma. Rev Esp Patol 2023; 56(3): 147-57.
[http://dx.doi.org/10.1016/j.patol.2023.02.005] [PMID: 37419553]
[19]
Ng WK, Yazan LS, Ismail M. Thymoquinone from Nigella sativa was more potent than cisplatin in eliminating of SiHa cells via apoptosis with down-regulation of Bcl-2 protein. Toxicol In Vitro 2011; 25(7): 1392-8.
[http://dx.doi.org/10.1016/j.tiv.2011.04.030] [PMID: 21609759]
[20]
Rahman N, Khan H, Zia A, et al. Bcl-2 Modulation in p53 Signaling Pathway by Flavonoids: A Potential Strategy towards the Treatment of Cancer. Int J Mol Sci 2021; 22(21): 11315.
[http://dx.doi.org/10.3390/ijms222111315] [PMID: 34768743]
[21]
Khan A, Rehman MU. Black Seeds (Nigella sativa): Pharmacological and Therapeutic Applications. Amsterdam: Elsevier 2021.
[22]
Mylliemngap BJ, Borthakur A, Velmurugan D, Bhattacharjee A. In silico analysis and molecular docking of resuscitation promoting factor B (RpfB) protein of Mycobacterium tuberculosis. Bioinformation 2012; 8(14): 646-51.
[http://dx.doi.org/10.6026/97320630008646] [PMID: 23055604]
[23]
Suresh V, Sruthi V, Padmaja B, Asha VV. In vitro anti-inflammatory and anti-cancer activities of Cuscuta reflexa Roxb. J Ethnopharmacol 2011; 134(3): 872-7.
[http://dx.doi.org/10.1016/j.jep.2011.01.043] [PMID: 21295129]
[24]
Vadwai V, Devaraj S. In silico analysis of homocamptothecin (hCPT) analogues for anti-tumor activity. Int J Bioinform Res Appl 2009; 5(6): 603-15.
[http://dx.doi.org/10.1504/IJBRA.2009.029041] [PMID: 19887335]
[25]
Schapira M, Raaka BM, Samuels HH, Abagyan R. In silico discovery of novel retinoic acid receptor agonist structures. BMC Struct Biol 2001; 1(1): 1-7.
[http://dx.doi.org/10.1186/1472-6807-1-1] [PMID: 11405897]

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