Benzoic acid, 4-hydroxy-, methyl ester from Smilax zeylanica Linn emerges as a potent inhibitor of CD27/CD70 signaling pathway

Abstract

Smilax zeylanica Linn is explored as a natural solution to inhibit the CD27/CD70 interaction crucial in T and B cell responses. This plant-based approach offers a cost-effective and promising drug candidate for overcoming challenges associated with anti-CD27 antibodies. The plants were macerated in an ethanol solution, and the cytotoxicity of crude extracts was determined using the MTT assay on Vero cell lines. Preliminary antiviral activity against the lentivirus plasmid was analyzed using plaque reduction assays for both ethanol and methanol fractions of the ethanol extract. Additionally, the methanol fraction underwent phytochemical analysis via GC-MS. Molecular docking with the CD27 receptor was carried out using Autodock Vina, followed by a 100 ns Molecular dynamics simulation with Gromacs. The expression of CD27 in MCF-7 was assessed by flow cytometry using the compound benzoic acid, 4-hydroxy-, methyl ester. On Vero cell lines, the ethanol extract was nontoxic. Furthermore, at 100 µg/ml, the ethanol extract and its methanol fraction showed percentage inhibitions of 64% and 66% in the plaque reduction assay. In addition, 22 chemicals were identified by GC-MS analysis of the ethanol extract’s methanol fraction. Molecular Docking benzoic acid, 4-hydroxy-methyl ester of methanol fraction revealed the highest binding affinity with CD27. Molecular dynamics simulations of benzoic acid, 4-hydroxy-, methyl ester showed structure stability for a duration of 100 nanoseconds, Moreover, at a dosage of 50 µg/ml, benzoic acid, 4-hydroxy-, methyl ester was found to reduce CD27 expression in MCF-7 cells by 73.65% using flow cytometry. Communicated by Ramaswamy H. Sarma