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Computational Examination of Curcumin Derivatives as Promising Inhibitors for BRCA1 and BRCA2 Proteins in Breast Cancer Treatment

Srisai Inampudi

Abstract


 

Objective: Breast cancer is a major problem for global health and one of the most popular and dangerous diseases. Data from the National Cancer Registry Program (NCRP) of the National Center for Disease Informatics and Research (NCDIR), an arm of the Indian Council of Medical Research (ICMR) in Bangalore, India, shows that an estimated 1,461,427 new cancer cases will occur… Conditions in India by 2022. Among these conditions, breast cancer in men and breast cancer in women emerged as the most common types of cancer. The present analysis demonstrates the discovery of new drugs by selecting BRCA1(1JNX) and BRCA2(1N0W) targets for molecular docking with derivatives of the medicinal plant Curcuma longa. This study investigates the pharmacological properties of the drug and examines its therapeutic potential.

 Methods: In this study, computational methods were used to evaluate the inhibitory potential of different plants against BRCA1 and BRCA2 target proteins. Perform protein molecular docking using a variety of tools, including IMPAAT, PubChem, PDB, ADME, ADMETlab 2.0, Pyrx, BIOVIA Discovery Studio Visualizer, PDB sum, and EMBL pep window. Result: Docking results showed that the selected ligand had the best affinity for BRCA1 and BRCA2 proteins.

 Conclusion: The ligands found in this study can be used in the future to study their effectiveness as anti-cancer drugs. In addition, in vitro and in vivo studies can be conducted to evaluate the inhibitory potential of these ligands and to develop new anti-cancer drugs.


Keywords


Breast cancer, Curcuma longa, BRCA1, BRCA2, Molecular Docking, ADMET,

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References


Sathishkumar K, Chaturvedi M, Das P, Stephen S, Mathur P. Cancer incidence estimates for 2022 & projection for 2025: Result from National Cancer Registry Programme, India. The Indian Journal of Medical Research [Internet]. 2022 Dec 13; Available from: https://pubmed.ncbi.nlm.nih.gov/36510887/#:~:text=Results%3A%20The%20estimated%20number%20of

Sharma GN;Dave R;Sanadya J;Sharma P;Sharma KK; Various types and management of breast cancer: An overview [Internet]. U.S. National Library of Medicine; [cited 2024 Jan 16]. Available from: https://pubmed.ncbi.nlm.nih.gov/22247839/

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: a Cancer Journal for Clinicians. 2021 Feb 4;71(3):209–49.

Sun YS, Zhao Z, Yang ZN, Xu F, Lu HJ, Zhu ZY, et al. Risk Factors and Preventions of Breast Cancer. International Journal of Biological Sciences [Internet]. 2017 Nov 1;13(11):1387–97. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5715522/

Gerhardus A, Schleberger H, Schlegelberger B, Gadzicki D. Diagnostic accuracy of methods for the detection of BRCA1 and BRCA2 mutations: a systematic review. European Journal of Human Genetics [Internet]. 2007 Jun 1 [cited 2021 Mar 18];15(6):619–27. Available from: https://www.nature.com/articles/5201806#Abs1

Zeng L, Yang K, Hao W, Yu G, Chen H. The efficacy and safety of Curcuma longa Extract and curcumin supplements on osteoarthritis: a systematic review and meta-analysis. Bioscience Reports. 2021 May 21;41(6).

Farghadani R, Naidu R. Curcumin as an Enhancer of Therapeutic Efficiency of Chemotherapy Drugs in Breast Cancer. International Journal of Molecular Sciences. 2022 Feb 15;23(4):2144.

Teng DH, Bogden R, Mitchell J, Baumgard M, Bell R, Berry S, et al. Low incidence of BRCA2 mutations in breast carcinoma and other cancers. Nature Genetics [Internet]. 1996 Jun 1 [cited 2022 Sep 23];13(2):241–4. Available from: https://pubmed.ncbi.nlm.nih.gov/8640236/

Smith TM, Lee MK, Szabo CI, Jerome N, McEuen M, Taylor M, et al. Complete genomic sequence and analysis of 117 kb of human DNA containing the gene BRCA1. Genome Research [Internet]. 1996 Nov 1 [cited 2021 Nov 9];6(11):1029–49. Available from: https://genome.cshlp.org/content/6/11/1029.full.pdf

Williams RS, Green R, Glover JNM. Crystal structure of the BRCT repeat region from the breast cancer-associated protein BRCA1. Nature Structural Biology. 2001 Oct 1;8(10):838–42.

Pellegrini L, Yu DS, Lo T, Anand S, Lee M, Blundell TL, et al. Insights into DNA recombination from the structure of a RAD51–BRCA2 complex. Nature [Internet]. 2002 Nov [cited 2019 Sep 10];420(6913):287–93. Available from: https://www.nature.com/articles/nature01230

Godet I, M. Gilkes D. BRCA1 and BRCA2 mutations and treatment strategies for breast cancer. Integrative Cancer Science and Therapeutics [Internet]. 2017;4(1). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5505673/

Kashyap D, Pal D, Sharma R, Garg VK, Goel N, Koundal D, et al. Global Increase in Breast Cancer Incidence: Risk Factors and Preventive Measures. Teekaraman Y, editor. BioMed Research International [Internet]. 2022 Apr 18;2022:1–16. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9038417/

Acharya R, Chacko S, Bose P, Lapenna A, Pattanayak SP. Structure Based Multitargeted Molecular Docking Analysis of Selected Furanocoumarins against Breast Cancer. Scientific Reports. 2019 Oct 31;9(1).

Jones ME, Schoemaker MJ, Wright LB, Ashworth A, Swerdlow AJ. Smoking and risk of breast cancer in the Generations Study cohort. Breast Cancer Research [Internet]. 2017 Nov 22 [cited 2019 Jun 25];19(1). Available from: https://dx.doi.org/10.1186%2Fs13058-017-0908-4

Starek-Świechowicz B, Budziszewska B, Starek A. Alcohol and breast cancer. Pharmacological Reports. 2022 Oct 30;

Roy R, Chun J, Powell SN. BRCA1 and BRCA2: different roles in a common pathway of genome protection. Nature Reviews Cancer. 2012 Jan;12(1):68–78.

Riaz A, Rasul A, Kanwal N, Hussain G, Shah MA, Sarfraz I, et al. Germacrone: A Potent Secondary Metabolite with Therapeutic Potential in Metabolic Diseases, Cancer and Viral Infections. Current Drug Metabolism. 2020 Dec;21(14):1079–90.

Pina S, Thallita Kelly Rabelo, Gabriela G.G. Trindade, Almeida S, Marlange Almeida Oliveira, Santos PL, et al. γ-Terpinene complexed with β-cyclodextrin attenuates spinal neuroactivity in animals with cancer pain by Ca2+ channel block. Journal of Pharmacy and Pharmacology. 2022 Aug 17;74(11):1629–39.




DOI: https://doi.org/10.37591/rrjocb.v12i3.3370

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