Abstract

IN SILICO MOLECULAR DOCKING OF DI-(2-ETHYLHEXYL) PHTHALATE AND 13-HEXYLOXACYCLOTRIDEC-10-EN-2-ONE IDENTIFIED IN AMBROSIA MARITIMA L. (ASTERACEAE)

Amina I. Dirar, Magdi A. Mohamed*, Esraa M.O. Ismail, Hassan S. Khalid,
Fatima Alfatih and Asaad Khalid

Abstract

Discovery of new lead compounds to compact diseases can be traced directly to medicinal plants. In silico studies provide a good platform to estimate the applicability of various virtual screening methods in the assessment of a desired biological activity. This study was carried out to identify the bioactive compounds' relevant targets and to establish their therapeutic effects on molecular level. Two compounds namely, di-(2-ethylhexyl) phthalate (DEHP) and 13- hexyloxacyclotridec-10- en-2-one, were identified in the previously bio-assessed active Ambrosia maritima's extract. The lead compounds' relevant targets were identified via the SwissTargetPrediction tool. The molecular docking was preformed via Auto-Dock 4.0 software. In structural bases virtual screening for target enzymes, Protein Kinase C Gamma Type (PKCG) and Cytochrome P450 19A1 (CYP19A1) ranked the top in binding probability for DEHP and 13-hexyloxacyclotridec-10-en-2-one, respectively. Molecular docking of DEHP on PKCG revealed a free binding energy of-5.75 Kcal/mol and showed three hydrogen bonds with the amino acid residue Arginine 185 and hydrophobic interactions. Docking of the other compound on CYP19A1 showed hydrogen bond with the amino acid residue Threonine 310, hydrophobic interaction and the free binding energy was -8.33 Kcal/mol. Thus, hit compounds predicted by in silico investigations in conjunction with ethnomedicinal approaches are likely to confer new chemical entities with potential chemotherapeutic properties.

Keywords: Ambrosia maritima, di-(2-ethylhexyl) phthalate, 13- hexyloxacyclotridec-10-en-2-one, Protein kinase C gamma, Cytochrome P450 19A1, SwissTargetPrediction, Auto-Dock 4.0.