Title

Authors

Affiliation

¹Department of Bioinformatics, School of Life Sciences, Karpagam University, Coimbatore 641021, India; ²Department of Bioinformatics, SIAS-Centre for Scientific, Research, Safi Institute of Advanced Study(SIAS) , Rasiya Nagar, Vazhayoor East, Malappuram-673633, Kerala, India; ³Research and Development centre, Bharathiyar University,Coimbatore.641046,Tamilnadu; ⁴Bioinformatics Research Laboratory, Eminent Biosciences, Vijaynagar, Indore - 452010, India; ⁵Department of Biochemistry, PSG College of Arts and Science, Coimbatore - 641 014, India

Email

victordoss64@hotmail.com; *Corresponding author

Article Type

Hypothesis

Date

Received May 09, 2015; Revised May 25, 2015; Accepted June 04, 2015; Published June 30, 2015

The present antipsychotic drugs have known to show serious concerns like extra pyramidal side effects therefore, pursuit for novel antipsychotic GABAnergic drugs has lately focused on the folkloric medicine from plant derivatives as better treatment option of schizophrenia. The present study centers to identify potential inhibitors of plant origin for GABA receptor through in silico approaches. Three compound datasets were undertaken in the study. The first set consisted of seven compounds which included Magnolol, Honokiol and other plant derivatives. The second set consisted of 16 derivatives of N-diarylalkenyl-piperidinecarboxylic acid synthesized by Zheng et al., 2006. The third dataset had thirty two compounds which were Magnolol and Honokiol analogues synthesized by Fuchs et al., 2014. All the compounds were docked at the allosteric site of the GABA (A) receptor. The compounds were further tested for ADMET and biological activity. We observed Honokiol and its derivatives demonstrated superior druglike properties than any compound undertaken in the study. Further, compound 61 [2-(4-methoxyphenyl)-4-propylphenol] of dataset three - a synthetic derivative of honokiol had better profile than its parent compound. In a possible attempt to identify compound with even better efficacious compound than 61, virtual screening was performed, 135 compounds akin to compound 61 were retrieved. Interestingly none of the 135 compounds showed better druggable properties than compound 61. Our in silico pharmacological profiling of compounds is in coherence and is complemented by the findings of Fuchs et al, which also revealed compound 61 to be the good potentiator of GABA receptor.

Keywords

Schizophrenia, Plant derivatives, GABA inhibitors, in silico Pharmacological profiling

Abbreviations

GABA (A) R: Gamma Amino Butyric Acid Receptor, subtype A; GPCR: G Protein Coupled Receptor; OPLS: Optimized Potentials for Liquid Simulations; PDB: Protein Data Bank; PLP: Piece wise Linear Potential; T.E.S.T: Toxicity Estimation Software Tool; TCM: Traditional Chinese Medicine

Citation

Sahila et al. Bioinformation 11(6): 280-289 (2015)
 

Edited by

P Kangueane

ISSN

0973-2063

Publisher

Biomedical Informatics

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.