Journal of Proteomics & Bioinformatics
Open Access

Trypanocidal activity of new benzoic acid derivatives as potential trans-sialidase inhibitors and their pharmacoproteomics study

6^th International Conference & Expo on Proteomics

March 29-31, 2016 Atlanta, USA

Muhammad Kashif

Instituto Politecnico Nacional, Mexico

Posters & Accepted Abstracts: J Proteomics Bioinform

Abstract :

This work describes a series of benzoic acid derivatives as potential anti-trypanosomal agents and trans-sialidase (TS) inhibitors. Para-amino and Para-acetamido-meta-nitro benzoic acid compounds showed moderate trypanocidal activity against INC-5 strain (114.8 and 48.2 �?¼M, respectively) and highest TS inhibitory activity at 1.0 mM (77 and 66%, respectively). Ethyl benzoate derivatives and Para-amino-ortho-hydroxylbenzoic acid compound showed high trypanocidal assays against NINOA (<71.4 �?¼M) and INC-5 (<56.8 �?¼M) strains, but lower inhibitory activity (<47%). It is noteworthy that ethyl 4-(4-chlorobenzamido)-3-nitrobenzoate showed nanomolar trypanocidal activity against INC-5 strain (280 nM). The respective docked structure of compounds showed three different binding patterns according to DANA crystal structure in the active site cavity. Model A is similar to DANA interaction in the cavity, Model B presented the opposite binding conformation whereas model C is interacting outside the cavity which is associated to the lowest binding scores and lower inhibition results. Therefore, predictive docking should be considered for in silico screening experiments. Pharmacoproteomics study was carried out by MALDI-TOF and these derivatives are found to be excellent inhibitor and inhibit the activity of target trans-sialidase enzyme about (60%) and good relationship found between chemical probe and efficacy of these derivatives. Taken together, these data highlights the ethyl 4-acetamido-3-nitrobenzoate as a prototype for the development of more effective TcTS inhibitors against Chagas disease showing a binding model similar to DANA (pattern A), moderate inhibition to TcTS (47%) and significant trypanocidal activity (7.3 and 56.8 �?¼M against NINOA and INC-5 strains, respectively).

Biography :

Muhammad Kashif is currently pursuing his PhD at Insituto Politecnico Nacional, Mexico. He is a Research Associate at the Islamia University, Bhawalpur, Pakistan. He has published over 5 papers in reputable journals.

Email: chkashif987@gmail.com