Molecular docking analysis of lupeol with different cancer targets.

ISSN 0973-2063 (online) 0973-8894 (print) ©Biomedical Informatics (2022) Bioinformation 18(3): 134-140 (2022) www.bioinformation.net Volume 18(3) Research Article Received January 3, 2022; Revised March 30, 2022; Accepted March 31, 2022, Published March 31, 2022 DOI: 10.6026/97320630018134 Declaration on Publication Ethics: The author’s state that they adhere with COPE guidelines on publishing ethics as described elsewhere at https://publicationethics.org/. The authors also undertake that they are not associated with any other third party (governmental or non-governmental agencies) linking with any form of unethical issues connecting to this publication. The authors also declare that they are not withholding any information that is misleading to the publisher in regard to this article. 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Bioinformation 18(3): 134-140 (2022) Molecular docking analysis of lupeol with different cancer targets Mahalakshmi Gunasekaran*, Ravali Ravi & Kavimani Subramanian Department of Pharmacology, College of Pharmacy, Mother Theresa Post Graduate and Research Institute of Health Science, Pondicherry University, Puducherry-605006, India; *Corresponding author: Author contacts: Mahalakshmi Gunasekaran - E-mail: Kavimani Subramanian – E-mail: Ravali Ravi– E-mail: Abstract: Lupeol is one of the secondary metabolite (triterpenoid) present in many medicinally effective plants. It has numerous biological and pharmacological actions. Lupeol is found to have effective herbs and has immense biological activity against several diseases including its cytotoxic effect on cancer cells. In recent drug designing, molecular study of analysis is usually used for understanding the target and the ligand interaction. Therefore, it is of interest to document the molecular docking analysis data of lupeol with different cancer targets such as Caspase- 3, BCL-2, Topoisomerase, PTK, mTOR, H-Ras, PI3K, AKT. These molecular docking studies were carried out by using AutoDock tools 4.2 version software. Molecular docking analyses of lupeol with target protein were found to have good dock score and 134 ISSN 0973-2063 (online) 0973-8894 (print) ©Biomedical Informatics (2022) Bioinformation 18(3): 134-140 (2022) minimum inhibition constant. BCL-2, Topoisomerase, PTK, mTOR and PI3Kdocking studies showed the best binding energy inhibition constant and ligand efficiency. The in-silico molecular docking analysis showed that the lupeol having relatively good docking energy, affinity and efficiency towards the active macromolecule, thus it may be considered as good inhibitor of proliferating cancer cells. By this knowledge of docking results, the lupeol can be used as promising drug for anticancer activity. Keywords: Molecular docking, lupeol, cancer targets Background: Lupeol is a penta cyclic tri terpenoid, present in most of the effective herbs and exhibits an immense biological activity against human ailnments [1, 2]. Lupeol has cytostatic effects on cancer cells through modulation of expression of IL-2, IL4, IL5, ILβ, proteases, α-glucosidase, cFLIP, and NFκB [2-5].Also significantly induces cell deaths through altering the expression levels of BCL-2, BAX, caspases, and PI3K-AKT-mTOR signaling pathway in cancer cells [1,5-7]. It modulates the molecules such as Cyclins, CDKs, P53, P21, PCNA, cdc25C, and plk1 which were involved in cell cycle regulation in different cancer types [7, 8].Cancer cells have a characteristic metabolism, mostly caused by alterations in signal transduction networks rather than mutations in metabolic enzymes [9].To develop targeted therapies, identification of the genetic changes that help a tumor to grow and change is necessary. A potential target would be a protein that is present only in cancer cells but not healthy cells. This can be caused by a mutation. Targeted therapy in cancer inhibits the signaling pathway of the targets which carry information regarding enhanced cell growth. Many research works on the anticancer activity of lupeol has been reported. Not many reports have been published on the in-silico docking approach. So an attempt has been made to study the clear mechanism of action with the aid of in-silico approaches. Few target proteins like Caspase-3, BCL-2, Topoisomerase, Protein tyrosine kinases (PTK), Phosphatidylinositol-3-kinase (PI3k), and Mammalian or Mechanistic target of rapamycin (mTOR), AKT, Hras. Caspase-3 is an endoprotease enzyme that coordinates the destruction cellular structures like DNA fragmentation and degradation of cytoskeletal proteins. Caspases are essential in the dismantling processes of the cell and the formation of apoptotic bodies [10-12].The deregulation of caspase-3 leads to cancer.BCL-2 is B-cell lymphoma 2, encoded in humans by the BCL-2 gene that regulates apoptosis. An unbalanced state between pro- versus antiapoptotic BCL-2 proteins can act as a barrier to apoptosis and facilitate cancer development [13, 14]. Topoisomerases are one of the most important cancer chemotherapy targets [15, 16]. These enzymes play a crucial role for cell function and perform a wide range of functions like maintenance of DNA topology in DNA replication, and transcription. Protein tyrosine kinase (PTK) is one of the major signaling enzymes in the process of cell signal transduction that regulates cell growth and differentiation [17-19]. Aberration in this pathway leads to various forms of cancer [20]. Over 40 chromosomal translocations with of 12 different PTK deregulated signaling were associated with various hematologic malignancies [21]. Phosphoinositide 3-kinase (PI3K) and its subtypes regulate AKT signaling pathway with the help of numerous stimuli and kinases present in the cell which leads cellular growth and survival [22-24]. mTOR with other key components catalyzes the phosphorylation of multiple targets such as ribosomal protein S6 kinase β-1 (S6K1), eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), AKT, protein kinase C (PKC), and type-I insulin-like growth factor receptor (IGF-IR), and regulates protein synthesis, nutrients metabolism, growth factor signaling, cell growth, and migration. Thus deregulation of mTOR leads to tumor growth and metastasis [25-27]. The Akt (serine/threo (...truncated)