title: Molecular modeling and snake venom phospholipase A2 inhibition by phenolic compounds: Structure-activity relationship.
abstract: In our earlier study, we have reported that a phenolic compound 2-hydroxy-4-methoxybenzaldehyde from Janakia arayalpatra root extract was active against Viper and Cobra envenomations. Based on the structure of this natural product, libraries of synthetic structurally variant phenolic compounds were studied through molecular docking on the venom protein. To validate the activity of eight selected compounds, we have tested them in in vivo and in vitro models. The compound 21 (2-hydroxy-3-methoxy benzaldehyde), 22 (2-hydroxy-4-methoxybenzaldehyde) and 35 (2-hydroxy-3-methoxybenzylalcohol) were found to be active against venom-induced pathophysiological changes. The compounds 20, 15 and 35 displayed maximum anti-hemorrhagic, anti-lethal and PLA2 inhibitory activity respectively. In terms of SAR, the presence of a formyl group in conjunction with a phenolic group was seen as a significant contributor towards increasing the antivenom activity. The above observations confirmed the anti-venom activity of the phenolic compounds which needs to be further investigated for the development of new anti-snake venom leads.
authors.affiliation: Department of Physiology, Hamdard Institute of Medical Sciences & Research, Jamia Hamdard, New Delhi, 110062, India. Electronic address: iqbalasc@yahoo.com.
authors.forename: Md Iqbal
authors.initials: MI
authors.lastname: Alam
authors.affiliation: National Brain Research Center, Manesar, Gurgaon, India.
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Alam
authors.affiliation: Department of Pharmaceutical Chemistry, Jamia Hamdard, New Delhi, 110062, India.
authors.forename: Ozair
authors.initials: O
authors.lastname: Alam
authors.affiliation: Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Nargotra
authors.affiliation: Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, India.
authors.forename: Subhash Chandra
authors.initials: SC
authors.lastname: Taneja
authors.affiliation: Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, India.
authors.forename: Surrinder
authors.initials: S
authors.lastname: Koul
mesh_terms: D000997:Antivenins / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008958:Models, Molecular; D015394:Molecular Structure; D010636:Phenols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D064801:Phospholipase A2 Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D054467:Phospholipases A2 / Q000378:metabolism*; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry; D012910:Snake Venoms / Q000201:enzymology*; D013329:Structure-Activity Relationship
chemical_list: D000997:Antivenins; D001688:Biological Products; D010636:Phenols; D064801:Phospholipase A2 Inhibitors; D010936:Plant Extracts; D012910:Snake Venoms; D054467:Phospholipases A2
keywords: 2-hydroxy-3-methoxybenzyl alcohol; Antisnake venom activity; PLA(2) inhibitors; Phenolic compounds; SAR