SYNTHESIS, CHARACTERIZATION, AND MOLECULAR DOCKING ANALYSIS OF PROLINE (PYRROLIDINE 2-CARBOXYLIC ACID) AND PROLINAMIDE (PYRROLIDINE 2-CARBOXYLIC ACID AMIDE) ISOMERS AS BACTERIAL COLLAGENASE INHIBITORS

Kavya Sundararaju; Ramesh Kumar Chidambaram; Radhakrishnan Narayanaswamy

doi:10.22159/ajpcr.2019.v12i1.29894

Authors

Kavya Sundararaju Department of Chemistry, Organic Chemistry Lab, Vel Tech Rangarajan Dr. Sagunthala R and D Institute of Science and Technology, Avadi, Chennai, Tamil Nadu, India.
Ramesh Kumar Chidambaram Department of Chemistry, Organic Chemistry Lab, Vel Tech Rangarajan Dr. Sagunthala R and D Institute of Science and Technology, Avadi, Chennai, Tamil Nadu, India.
Radhakrishnan Narayanaswamy Bio Incubator, Vel Tech Technology Incubator, Chennai, Tamil Nadu, India.

DOI:

https://doi.org/10.22159/ajpcr.2019.v12i1.29894

Keywords:

Molecular docking, Proline, Prolinamide isomers, PatchDock, Clostridium histolyticum collagenase inhibitors

Abstract

Objectives: D-proline is an isomer of L-proline, naturally occurring amino acid. Apart from this, several proline homologs and analogs are available in nature. For instance, hydroxyproline one of proline analog plays a key role in collagen function. Inhibition of collagenase activity plays a significant role in protecting the unbalanced turnover of collagen, caused due to inflammation and photoaging of skin. This prompted us to carry out the study on proline and prolinamide isomers.

Methods: These proline and prolinamide isomers were evaluated on the docking behavior of bacterial collagenase using PatchDock. In addition, molecular physicochemical, drug-likeness, absorption, distribution, metabolism and excretion (ADME) analysis, synthesis, and characterization of four prolinamide isomers were also carried out.

Results: All the four synthesized prolinamide isomers showed >90% yield. The molecular physicochemical analysis revealed that proline and prolinamide isomers showed nil violation and complied well with the Lipinski's rule of five. ADME analysis showed that prolinamide isomers predicated to have bloodâ€“brain barrier permeability. Docking studies revealed that D (S, R) prolinamide isomer showed the maximum atomic contact energy (âˆ’115.09 kcal/mol) with that of Clostridium histolyticum collagenase.

Conclusion: Thus, the present study showed the potential of proline and prolinamide isomers as collagenase inhibitors.

Downloads

Download data is not yet available.

References

Nagata Y, Masui R, Akino T. The presence of free D-serine, D-alanine and D-proline in human plasma. Experientia 1992;48:986-8.

Nagata Y, Higashi M, Ishii Y, Sano H, Tanigawa M, Nagata K, et al. The presence of high concentrations of free D-amino acids in human saliva. Life Sci 2006;78:1677-81.

Gupta SK, Mandal P. Bioinformatics characterization of SOD under UV in fenugreek (Family: Fabaceae). Int J Pharm Pharm Sci 2016;8:231-7.

Wagner I, Musso H. New naturally occurring amino acids. Angew Chem Int Ed Engl 1983;22:816-28.

Burnett CL, Heldreth B, Bergfeld WF, Belsito DV, Hill RA, Klaassen CD, et al. Safety assessment of Î±-amino acids as used in cosmetics. Int J Toxicol 2013;32:41S-64.

Haraya N, Oshimura E. Moisturizer and Cosmetic Containing Same. Patent 9782336. US: Ajinomoto Co., Inc.; 2017.

Roso A, Garcia C. Cosmetic and Pharmaceutical Compositions Comprising Lauroyl Proline and an Ester of Anhydrohexitol and of an Aliphatic Carboxylic Acid. Patent 8093221. US; 2012.

Wu X, He C, Wu X, Qu S, Duan C. An L-proline functionalized metallo-organic triangle as size-selective homogeneous catalyst for asymmetry catalyzing aldol reactions. Chem Commun (Camb) 2011;47:8415-7.

Jiangwei X, Xiangkai F, Chuanlong W, Xiaoyan H. Simple, inexpensive, and facile L-prolinamide used as a recyclable organocatalyst for highly efficient large-scale asymmetric direct aldol reactions. Tetrahedron Asymmetry 2011;22:840-50.

Vijayakumar V, Radhakrishnan N, Rameshkumar C. Molecular Docking Analysis of Imidazole Derivatives and Polybenzimidazole Analogues as Inhibitors of Superoxide Dismutase (SOD) and Xanthine Oxidase (XO). IEEE International Conference on Smart Technologies and Management for Computing, Communication, Controls, Energy and Materials (ICSTM); 2017. p. 513-6.

Radhakrishnan N. Molecular docking analysis of alginate oligosaccharides (Alg2-Alg6) as bacterial collagenase inhibitor. J Appl Cosmetol 2017;35:15-23.

Radhakrishnan N, Lam KW, Faridah A, Intan IS. Molecular docking analysis of curcumin analogues elastase (HNE) inhibitors. Bangladesh J Pharm 2014;9:77-82.

Daina A, Michielin O, Zoete V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 2017;7:42717.

Schneidman-Duhovny D, Inbar Y, Nussinov R, Wolfson HJ. PatchDock and SymmDock: Servers for rigid and symmetric docking. Nucleic Acids Res 2005;33:W363-7.

Rojas J, Londono C, Ciro Y. The health benefits of natural skin UVA photoprotective compounds found in botanical sources. Int J Pharm Pharm Sci 2016;8:13-23.

Radhakrishnan N, Lam KW, Intan IS. In silico analysis of selected honey constituents as human neutrophil elastase (HNE) and matrix metalloproteinases (MMP 2 and 9) inhibitors. Int J Food Prop 2015;18:2155-64.

Singh S, Gupta AK, Verma A. Molecular properties and bioactivity score of the Aloe vera antioxidant compounds â€“ In order to lead finding. Res J Pharm Biol Chem Sci 2013;4:876-91.

Akdogan ED, Erman B, Yelekci K. In silico design of novel and highly selective lysine-specific histone demethylase inhibitors. Turk J Chem 2011;35:523-42.

Cheng XC, Wang Q, Fang H, Xu WF. Advances in matrix metalloproteinase inhibitors based on pyrrolidine scaffold. Curr Med Chem 2008;15:374-85.