Original Article EXPLORATION OF ANTI-MELANOMA POTENTIAL OF PHYTOCHEMICALS FROM NYCTANTHES ARBORTRISTIS THROUGH COMPUTATIONAL STUDIES SHARMISTHA BANERJEE 1 , MEENAKSHI BHARKATIYA 2 , SURADA PRAKASH RAO 3 , ISHITA BAGHEL 4 , MADHURI BAGHEL 5* 1 BME and BI, UTD, Chhattisgarh Swami Vivekanand Technical University, Newai, Bhilai, CG-491107, India. 2 Bhupal Nobles Institute of Pharmaceutical Sciences, Bhupal Nobles University, Udaipur-313001, India. 3 Columbia Institute of Pharmacy, Raipur, CG, India. 4 Foothill High School, 4375, Foothill Road, Pleasanton, CA-94588, India. 5 Apollo College of Pharmacy, Anjora, Durg, CG-491001, India * Corresponding author: Madhuri Baghel; * Email: banchhormadhuri@gmail.com Received: 08 Nov 2023, Revised and Accepted: 08 Jan 2024 ABSTRACT Objective: The goal of the current research is to identify the dominant phytochemical from the plant Nyctanthesarbor-tristis Linn. and to investigate their binding affinities against the proteins BRaf Kinase mutant (3OG7) and Hsp90 Chaperone (2VCJ) that causes melanoma. Methods: In this work, Schrodinger software was utilized to investigate the anti-cancer potential of phytochemicals Nyctanthesarbor-tristis against specific target proteins, namely BRaf Kinase mutant (3OG7) and Hsp90 Chaperone (2VCJ) Inhibitors. Results: Based on the outcome of the docking investigation, phytochemicals that exhibited the highest binding affinity to the specified protein targets were subjected to induced fit docking and MM-GBSA computations using the Schrodinger Maestro version 2021.2 in prime module. According to the analysis, the compounds with the highest binding affinities for 2VCJ and 3OG7 are Arbortristoside D and Nicotiflorin, respectively. The compound that interacted with both proteins was Arbortristoside B. These phytochemicals appear to be more effective to the FDA-approved V600E-BRaf inhibitor Vemurafenib and Hsp90 Chaperone Inhibitor Diclonine. Conclusion: One of the most common, deadly, and dangerous malignant diseases with a high global prevalence rate is melanoma (skin cancer). The present study may prove more helpful in developing an ideal targeted drug delivery system of phytochemicals obtained from plant Nyctanthesarbor-tristisfor treatment of melanoma. This suggests that these substances could be evolved into highly effective anti-melanoma drugs. Keywords: Skin cancer, Nyctanthesarbor-tristis, Dyclonine, Vemurafenib, Molecular docking, Induced fit docking © 2024 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/) DOI: https://dx.doi.org/10.22159/ijap.2024v16i2.49834 Journal homepage: https://innovareacademics.in/journals/index.php/ijap INTRODUCTION Malignant melanoma is an aggressive form of skin cancer that accounts for approximately 75% of skin cancer-related deaths worldwide [1, 2]. According to American Cancer Society, estimate for melanoma in the United States for 2023 was about 97,610 new cases of invasive and 89,070 cases of in-situ melanoma will be diagnosed in United States, while 7,990 (approx) people are expected to die of melanoma Melanoma will be leading cause of death world wide. Melanoma is reportedly affected by various environmental and genetic factors, such as ultraviolet exposure and carcinogenic BRAF mutations [3, 4]. Inspite of several available treatment modalities (surgery, radiation therapy, immunotherapy, and chemotherapy) [5, 6] to cure melanoma, phytochemicals have been recognized as better anti-cancer therapies to prevent or inhibit carcinogenesis because of its fewer side effects and better biocompatibility [7]. Synthetic chemicals are widely used as medicines in the treatment of diseases, encompassing various side effects. Different plants were explored as a source of bioactive agents for the treatment of ailments like cancer. Plants pose immense biological properties due to the presence of different chemical substances which perform several important physiological functions. Among 4,22,000 flowering plants reported from the whole world, more than 50,000 plants are reported to have medicinal and pharmacological uses. A rich diversity of medicinal plants is found in India [8]. Nyctanthesarbor-tristis (NTA) Linn. (Oleaceae), commonly known as ‘parijat’ is a common wild shrub flourishing in the sub-Himalayan tract in the states of Uttar Pradesh, Assam, Bengal, Madhya Pradesh and in the south upto Godavari [9]. NTA is a beautiful and fragrant plant. Its flowers bloom at night, drop off and fall early next morning for this reason, it is called as-sad tree‖. It is mainly characterized by the presence of phenylethanoid derivatives and iridoid derivatives. It is used in traditional medicine as stomachic, carminative, intestinal astringent, expectorant, in biliousness, piles, and various skin diseases and as hair tonic. It has also been reported to possess hepato-protective, anti-viral, antifungal and analgesic, anti-pyretic, ulcerogenic activities [10]. Juice of the leaf is used in chronic and bilious fever rheumatism as a laxative, diaphoretic and diuretic. The plant has been reported to be effective against leishmanial, viral and amoebic infections [11]. It is also been used in the Ayurvedic system of medicine for the cure of snake bite, bites of wild animals, cancer, sores, ulcers, dysentery, menorrhagia and obstinate sciatica. Leaves are responsible for some Central Nervous System (CNS) activities such as hypnotic, tranquilizing, local anesthetic antiasthmatic activities [12]. Vemurafenib has potent inhibitory effect and is selective for BRAF kinase [13]. It is used to treat diseases imposed on by V600E-BRAF. Despite these advances, a large number of patients experienced vemurafenib resistance, and reports have demonstrated keratoacanthoma and high rates of squamous cell carcinomas associated with identified inhibitors [14, 15]. HSP90 chaperones, including mutant B-raf, are essential for cell survival and advancement of malignancy. Thus, blocking HSP90 can effectively stop the signalling pathways that promote tumour growth and stop HSP90 from functioning in tumour cells [16]. Therefore, the current study focuses on targeting Hsp90 Chaperone protein 2VCJ and B-Raf Kinase mutant protein 3OG7. We investigated the anti-cancer properties of phytochemicals from NTA against these protein targets. Further, we performed structure-based screening of phytochemicals from NTA against skin cancer protein targets and combined molecular docking, quantum mechanical charge derivation (MMGBSA) in the binding site, followed by induced fit docking on the protein targets, which is responsible for producing melanoma cancer. MATERIALS AND METHODS Protein preparation and receptor grid generation The three-dimensional (3D) structures of melanoma target proteins were retrieved from RCSB with Protein Data Bank (PDB) ids2VCJ (Hsp90 International Journal of Applied Pharmaceutics ISSN- 0975-7058 Vol 16, Issue 2, 2024