eng Oriental Scientific Publishing Company Biomedical and Pharmacology Journal 0974-6242 2024-09-30 17 3 1769 1783 10.13005/bpj/2982 60741 article Ramu Samineni 1 Prasanthi Samathoti 2 Sampath A. Gouru 3 Anwar Khan 4 Preethi Priyadharshni SP 5 Kiran Manda 6 Department of Pharmaceutics, School of Pharmacy, Joy University, Raja Nagar, Vadakangulam, Near Kanyakumari, Tirunelveli, Tamil Nadu, India Department of Pharmaceutics, MB school of Pharmaceutical Sciences, Mohan Babu University, Sree Sainath Nagar, Rangampet, Tirupati, Andhra Pradesh Department of Quality Assurance, EQRX International Inc. Cambridge, Massachusetts, USA. Department of Pharmaceutics, ERA College of Pharmacy, ERA university, Sarfaraz Ganj, Lucknow U. P. India. Department of Pharmacognosy and Phytochemistry, School of Pharmacy, Haramaya University Shri Vishnu College of Pharmacy, Garagaparru Road, Kovvada, Bhimavaram, Andhra Pradesh Nonsteroidal anti-inflammatory drugs (NSAIDs) that specifically target the enzyme cyclooxygenase-2, or COX-2, which causes inflammation and discomfort, are known as COX-2 inhibitors. The objective of this work is to perform the anti-inflammatory activity, and molecular docking studies of compounds. We aim to develop new drug phytochemicals as anti-inflammatory agents targeting COX-2(PDB ID: 1CX2) for treatment. To find potential molecules, the PyRx 0.8 tool has been used to dock 37 potent molecules against COX-2 (PDB ID: 1CX2). The top scorer molecules (phytochemicals) (Dihydromyricetin, Catechin, Chlorogenic acid, Chrysin, and Emodin) were selected. Prior to further analysis, the compounds underwent thorough in vivo evaluation to assess their toxicity and anti-inflammatory properties. The results indicated that dihydromyricetin, catechin, and chlorogenic acid were the sole substances that exhibited both negligible acute toxicity and superior anti-inflammatory properties, surpassing the efficacy of diclofenac sodium, the established medicine. Among the compounds that were evaluated, Dihydromyricetin was shown to possess the most powerful anti-inflammatory properties due to its trihydroxy phenyl chroman-4-one substitution. Correlated to diclofenac (-8.5 Kcal/mol), dihydromyricetin and catechin showed significant bounden affinity, with the lowest binding free energies (-9.9 and -9.2 Kcal/mol) according to the computational study. This correlation between in silico and in vivo studies validated these compound’s powerful anti-inflammatory properties. https://biomedpharmajournal.org/vol17no3/in-silico-investigation-and-development-of-cyclooxygenase-2-1cx2-selective-inhibition-as-a-possible-anti-inflammatory-activity/ Anti-inflammatory COX-2 Molecular docking studies Potent phytochemicals