Molecular docking and QSPR of 5-O-acetylpinostrobin derivatives that inhibit ERα as breast cancer drug candidates

Widiyana, Anita Puspa; Widiandani, Tri; Siswodihardjo, Siswandono

doi:10.48309/ecc.2023.409000.1674

Document Type : Original Research Article

Authors

¹ Doctoral Program of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya 60155, Indonesia

² Department of Pharmacy, Faculty of Medicine, Universitas Islam Malang, Malang 65144, Indonesia

³ Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya 60155, Indonesia

10.48309/ecc.2023.409000.1674

Abstract

The development of new breast cancer drugs is carried out through Computer-Aided Drug Design. Molecular docking and the Quantitative-Structure Properties Relationship (QSPR) as a step to obtain more effective compounds, selective, and the most influential physicochemical parameters through structural modification. Structural modification through the addition of acetyl groups caused changes in the biological activity of the compound. The research aimed to discover breast cancer drug prediction and its relationship with QSPR 5-O-acetylpinostrobin derivatives. The anti-breast cancer prediction used AutoDock Tools with the ERα type (PDB: 6V87). The selected parameters include free energy binding and inhibition constants. The physicochemical properties and excretion parameters were determined via online pkCSM and SwissADME. The relationship between physicochemical properties and total clearance was determined based on the QSPR equation with SPSS. The results of molecular docking showed five compounds with free energy binding and minimum inhibition constant values, namely P1, P2, P3, P4, and P5, with free energy binding values of -7.86, -7.77, -7.57, -7.31, and -6.96 kcal/mol and inhibition constant values of 1.73, 2.02, 2.82, 4.37, and 7.88 mM, respectively. The best QSPR equation was (1/CLtot) = 0.130*nRB - 0.034*MR + 0.366*Log P + 1.534 (n = 20, r = 0.761, SE = 0.579, F = 7.331, .sig = 0.003). An increase in nRB and Log P values and a decrease in MR values affect the increase in total clearance. Based on the results of the study, the five 5-O-acetylpinostrobin derivative compounds have the potential to be synthesized and tested further in vitro.

Graphical Abstract

Keywords

Main Subjects

Computational Chemistry

References

[1] Y.T. Ngoc Nguyen, C. Duong-Dinh, H. Vu-Quang, L. T. Lan Dinh, T. Nguyen-Minh, N. Dinh Nguyen, A. Tu Nguyen, LC-ESI-QTOF-HRMS-based myxobacterial metabolite profiling for potential anti-breast cancer extracts, J. Med. Chem. Sci., 2023, 6, 2767–2777. [Crossref], [Publisher]

[2] P.A. Kalvanagh, Y.A. Kalvanagh, A new therapeutic approach based on silymarin in the treatment of breast cancer, 2023, 5, 75–85. [Crossref], [Publisher], [Pdf]

[3] F. Mohajer, G.M. Ziarani, A. Badiei, New advances on modulating nanomagnetic cores as the MRI-monitored drug release in cancer, J. Appl. Organomet. Chem., 2021, 1, 141-145. [Crossref], [Google Scholar], [Publisher]

[4] N. Yellasubbaiah, V. Velmurugan, QSAR modeling, molecular docking, and adme studies of novel 5-oxo-imidazoline derivatives as anti-breast cancer drug compounds against MCF-7 Cell Line, J. Med. Chem. Sci., 2023, 6, 3087–3112. [Crossref], [Publisher], [Pdf]

[5] O.E. Oyeneyin, T.G. Abayomi, N. Ipinloju, E.B. Agbaffa, D.D. Akerele, O.A. Arobadade, Investigation of amino chalcone derivatives as anti-proliferative agents against MCF-7 breast cancer cell lines-DFT, molecular docking and pharmacokinetics studies, Adv. J. Chem. Sect. A, 2021, 4, 288–299. [Crossref], [Google Scholar], [Publisher]

[6] Shagufta, I. Ahmad, S. Mathew, S. Rahman, Recent progress in selective estrogen receptor downregulators (SERDs) for the treatment of breast cancer, RSC Med. Chem., 2020, 11, 438–454. [Crossref], [Google Scholar], [Publisher]

[7] X. Lu, Y. Teng, X. Lin, M. Xiao, C. Liu, X. Chi, Y. Zhang, G. Luo, H. Xiang, Discovery of novel 2H-chromene-3-carbonyl derivatives as selective estrogen receptor degraders (SERDs): Design, synthesis and biological evaluation, Bioorg. Chem., 2021, 109, 104714. [Crossref], [Google Scholar], [Publisher]

[8] Siswandono, R. Widyowati, A. Suryadi, T. Widiandani, D. Prismawa, Molecular modeling, synthesis, and qsar of 5-O-acylpinostrobin derivatives as promising analgesic agent, Rasayan J. Chem., 2020, 13, 2559–2568. [Crossref], [Google Scholar], [Publisher]

[9] M.R.F. Pratama, H. Poerwono, S. Siswandono, Design and molecular docking of novel 5-O-Benzoylpinostrobin derivatives as anti-breast cancer, Thai J. Pharm. Sci., 2019, 43, 201–212. [Crossref], [Google Scholar], [Publisher]

[10] S. Asirvatham, E. Thakor, H. Jain, Morpholine and Thiomorpholine: A Privileged Scaffold Possessing Diverse Bioactivity Profile, J. Chem. Rev., 2021, 3, 247-272. [Crossref], [Google Scholar], [Publisher]

[11] O. Babafakruddin, H. Abdul Ahad, H. Chinthaginjala, K. Tarun, G.A. Kumar, G.G. Reddy, The Design of Soft Drugs: Basic Principles, Energetic Metabolite Methods, Approved Compounds, and Pharmaceutical Applications, J. Chem. Rev., 2022, 4, 241-254. [Crossref], [Publisher]

[12] Y. Ahmadyousefi, Bacteria-Derived Chemotherapeutic Agents for Cancer Therapy: A Brief Overview, Asian J. Green Chem., 2023, 7, 223–228. [Crossref], [Pdf], [Publisher]

[13] E.N. Praditapuspa, S. Siswandono, T. Widiandani, In silico analysis of pinostrobin derivatives from boesenbergia pandurata on ErbB4 kinase target and QSPR linear models to predict drug clearance for searching anti-breast cancer drug candidates, Pharmacogn. J., 2021, 13, 1143–1149. [Crossref], [Google Scholar], [Publisher]

[14] S. Siswandono, Kimia Medisinal Edisi ke-1. Airlangga University Press; Surabaya, 2016. [Publisher]

[15] Lionta, G. Spyrou, D. Vassilatis, Z. Cournia, Structure-based virtual screening for drug discovery: principles, applications and recent advances, Curr. Top. Med. Chem., 2021, 14, 1923–1938. [Crossref], [Google Scholar], [Publisher]

[16] P.A. Kalvanagh, Y.A. Kalvanagh, A new therapeutic approach based on silymarin in the treatment of breast cancer, Adv. J. Chem. Sect. B, 2023, 5, 75–85. [Crossref], [Publisher]

[17] D.N. Illian, A.P. Widiyana, A.R. Hasana, H.A.I. Maysarah, S.S. Mustaniroh, M. Basyuni, In silico approach: prediction of ADMET, molecular docking, and QSPR of secondary metabolites in mangroves, J. Appl. Pharm. Sci., 2022, 12, 21–29. [Crossref], [Google Scholar], [Publisher]

[18] S. Sharma, A short review of past, present, and future of metallocene and its derivatives as an effective therapeutic agent, J. Appl. Organomet. Chem., 2023, 3, 142-155. [Crossref], [Publisher]

[19] A.B. Mezoughi, W. Abdussalam-Mohammed, A.A.A. Abdusalam, Synthesis and molecular docking studies of some thiohydantoin derivatives as potential anticancer and antimicrobial agents, Adv. J. Chem. Sect. A, 2021, 4, 327–338. [Crossref], [Google Scholar], [Publisher]

[20] M.T. Ibrahim, A. Uzairu, Structure-based identification of some potential epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) with in-silico assessment of their pharmacokinetic features and qantum cemical calculations, Adv. J. Chem. Sect. A., 2022, 5, 333–334. [Crossref], [Publisher]

[21] L. Frye, S. Bhat, K. Akinsanya, R. Abel, From computer-aided drug discovery to computer-driven drug discovery, Drug Discov. Today: Technol., 2021, 39, 111–117. [Crossref], [Google Scholar], [Publisher]

[22] L.G. Ferreira, R.N. Dos Santos, G. Oliva, A.D. Andricopulo, Molecular docking and structure-based drug design strategies, Molecules., 2015, 20, 13384-13421. [Crossref], [Google Scholar], [Publisher]

[23] N.K. Patel, G. Jaiswal, K.K. Bhutani, A review on biological sources, chemistry and pharmacological activities of pinostrobin, Nat. Prod. Res., 2016, 30, 2017–2027. [Crossref], [Google Scholar], [Publisher]

[24] S. Dara, S. Dhamercherla, S.S. Jadav, C.M. Babu, M.J. Ahsan, Machine learning in drug discovery: a review. Artif. Intell. Rev., 2021, 55, 1947-1999. [Crossref], [Google Scholar], [Publisher]

[25] S. Kar, J. Leszczynski, Open access in silico tools to predict the ADMET profiling of drug candidates, Expert. Opin. Drug. Discov., 2020, 15, 1473–1487. [Crossref], [Google Scholar], [Publisher]

[26] A.S. Wiyono, Siswandono, N.W. Diyah, Molecular docking of 5-o-benzoylpinostrobin derivatives from Boesenbergia pandurata roxb. as anti-inflammatory, J. Public Health Africa, 2023, 14. [Crossref], [Google Scholar], [Publisher]

[27] S.L. Agustin, T. Widiandani, S. Hardjono, B.T. Purwanto, QSAR of acyl pinostrobin derivatives as anti-breast cancer against HER-2 receptor and their ADMET properties based on in silico Study, RJPT, 2022, 15, 4641-4648. [Crossref], [Google Scholar], [Publisher]

[28] Y. Liu, X. Yu, J. Chen, Quantitative structure–property relationship of distribution coefficients of organic compounds, SAR QSAR Environ. Res., 2020, 31, 585–596. [Crossref], [Google Scholar], [Publisher]

[29] S.H. Abdullahi, A. Uzairu, G.A. Shallangwa, S. Uba, Pharmacokinetics studies of some diaryl pyrimidinamine derivatives as anti-cancer agent : in-silico drug design and molecular docking, Adv. J. Chem. Sect. A, 2022, 5, 320–332. [Crossref], [Google Scholar], [Publisher]

[30] A.M. Hantosha, N.A. Rajab, F.T. Abachic, Synthesis, in silico ADMET, docking, antioxidant, antibacterial and antifungal evaluations of some pyrimidine derivatives, Eurasian Chem. Commun., 2023, 5, 216–227. [Crossref], [Publisher]

[31] A.B. Umar, Exploration of aticancer potential of novel pyrrolo [2,3-b] pyridine derivatives targeting V600E-BRAF kinase : molecular docking , Pharmacokinetic and DFT Studies, Adv. J. Chem. Sect. A, 2022, 5, 271–286. [Crossref], [Publisher]

[32] M. Yusuf, U. Chawla, N.H. Ansari, M. Sharma, Perspective on metal-ligand coordination complexes and improvement of current drugs for neurodegenerative diseases ( NDDs ), Adv. J. Chem. Sect. A, 2023, 6, 31–49. [Crossref], [Google Scholar], [Publisher]

Eurasian Chemical Communications

Molecular docking and QSPR of 5-O-acetylpinostrobin derivatives that inhibit ERα as breast cancer drug candidates

References

References

Volume 5, Issue 12
December 2023
Pages 1117-1126

Molecular docking and QSPR of 5-O-acetylpinostrobin derivatives that inhibit ERα as breast cancer drug candidates

References

References

Volume 5, Issue 12December 2023Pages 1117-1126

Volume 5, Issue 12
December 2023
Pages 1117-1126