title: Tyrosinase inhibition: conformational analysis based studies on molecular dynamics calculations of bipiperidine based inhibitors.
abstract: Two series of variably N-substituted biperidines were synthesized by condensing various acid chlorides, alkyl halides and anhydrides with 1,4-bipiperidine. The new compounds were tested as tyrosinase inhibitors and a structure-activity relationship (SAR) study was carried out. Potent inhibition was observed in the case of the 4'-methylbenzyl substitution on this atom (IC50 = 1.72 microM) with this compound being a lead for future drug design. Additionally, calculations of the important QSAR molecular descriptors were done on the biperidine analogues after their 2 ps molecular dynamics (MD) simulations using molecular mechanics force field (MMFF) approaches. Using MD simulations potential and total energies were calculated for the energy minimized models of bipiperidine and the most active analogs 2, 3, 4, 6, 8 and 10.
authors.affiliation: HEJ Research Institute of Chemistry, International Center for Chemical Sciences, University of Karachi, Karachi 75270, Pakistan. hassaan2@super.net.pk
authors.forename: Khalid M
authors.initials: KM
authors.lastname: Khan
authors.forename: Zafar S
authors.initials: ZS
authors.lastname: Saify
authors.forename: Mahmud T H
authors.initials: MT
authors.lastname: Khan
authors.forename: Naeem
authors.initials: N
authors.lastname: Butt
authors.forename: Ghulam M
authors.initials: GM
authors.lastname: Maharvi
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Perveen
authors.forename: Nida
authors.initials: N
authors.lastname: Ambreen
authors.forename: Muhammad I
authors.initials: MI
authors.lastname: Choudhary
authors.lastname: Atta-Ur-Rahman
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D007980:Levodopa / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors*; D010880:Piperidines / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D004791:Enzyme Inhibitors; D010880:Piperidines; D007980:Levodopa; D014442:Monophenol Monooxygenase