Synthesis, characterization, in-vitro pharmacological assessment and molecular docking studies of trigonelline derivatives

• Published in: JOURNAL OF MOLECULAR STRUCTURE
• Main Authors: Singh, Neetu; Yadav, Surender Singh; Kumar, Sanjiv; Narasihman, Balasubramanian; Ramasamy, Kalavathy; Lim, Siong Meng; Shah, Syed Adnan Ali
• Format: Article
• Language: English
• Published: ELSEVIER 2025
• Subjects: Chemistry
• Online Access: https://www-webofscience-com.uitm.idm.oclc.org/wos/woscc/full-record/WOS:001421782300001

Trigonella foenum-graecum (fenugreek) is one of the renowned spices, belonging to the family Fabaceae. The plant is popularly known for its various medicinal applications attributed to its diverse phytocompounds. Trigonelline is the principal phytocompound of trigonella that exhibits numerous pharmacological potentials. Therefore, trigonelline hydrazones have been synthesized and characterized by different spectral means. The newly synthesized derivatives were evaluated for their antibacterial (Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa and Escherichia coli), antifungal (Aspergillus oryzae and Fusarium oxysporum), antioxidant (DPPH and ABTS assays) and cytotoxic activities (SRB assay). The molecular docking and ADME parameters of newly synthesized derivatives were also studied. The antimicrobial study was carried out by disc-diffusion and broth dilution methods. Along with this, trigonella seed oil was also extracted (Soxhlet apparatus) and characterized by GC-MS analysis. Results revealed the highest antibacterial activity with T9 (ZIsa = 12.9 mm, MICbs = 12.5 mg/ mL), T5 (ZIsa = 12.2 mm, MICsa, bs, pa =12.5 mg/mL). The highest antifungal results were determined with T5 (ZIfo = 12.3 mm), and T9 (ZIfo = 12.4 mm), via disc-diffusion and broth-dilution assays. Compounds T5(% RSADPPH = 83.81, % RSAABTS = 89.68)andT9((% RSADPPH = 81.89, % RSAABTS = 85.16) were most potent antioxidant compounds. Cytotoxicity indicated the highest activity of compounds T5(IC50 = 20.6 mu g/mL)andT9 (IC50 = 26.1 mu g/mL) against HCT-116 cell lines. Compound T6was noticed with the highest docking score (-8.101 kcal/mol). Conclusively, T5 and T9 were found the most potent compounds and, therefore, can be used as lead therapeutic candidates in drug designing. Moreover, these compounds can be further validated pharmacologically by molecular dynamics, in-vivo and clinical trials.