Tyrosinase inhibition: Conformational analysis based studies on molecular dynamics calculations of bipiperidine based inhibitors.

Khan, Khalid M.; Saify, Zafar S.; Khan, Mahmud T. H.; Butt, Naeem; Maharvi, Ghulam M.; Perveen, Shahnaz; Ambreen, Nida; Choudhary, Muhammad I.; Atta-Ur-Rahman; Supuran, Claudiu T.

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'-methylbenzyi substitution on this atom (IC50 = 1-72 μM) 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.

PHENOL oxidase; MELANINS; MOLECULAR dynamics; ANIMAL pigments; PLANT pigments

Journal of Enzyme Inhibition & Medicinal Chemistry, 2005, Vol 20, Issue 4, p401

1475-6366

Academic Journal

10.1080/14756360500179333