title: Oxazolones: new tyrosinase inhibitors; synthesis and their structure-activity relationships.
abstract: The tyrosinase inhibitory potential of seventeen synthesized oxazolone derivatives has been evaluated and their structure-activity relationships developed in the present work. All the synthesized derivatives, 3-19, demonstrated excellent in vitro tyrosinase inhibitory properties having IC50 values in the range of 1.23+/-0.37-17.73+/-2.69 microM, whereas standard inhibitors l-mimosine and kojic acid have IC50 values 3.68+/-0.02 and 16.67+/-0.52 microM,, respectively. Compounds 4-8 having IC50 values 3.11+/-0.95, 3.51+/-0.25, 3.23+/-0.66, 1.23 +/- 0.37, and 2.15+/-0.75, respectively, were found to be very active members of the series, even better than both the standard inhibitors. However, compounds 3, 9-11, 13, 14, 16, 17, and 19 were found to be better than kojic acid but not l-mimosine. (2-Methyl-4-[E,2Z)-3-phenyl-2-propenyliden]-1,3-oxazol-5(4H)-one (7) bearing a cinnamyol residue at C-4 of oxazolone moiety and an IC50 = 1.23+/-0.37 microM was found to be the most active one among all tested compounds. These studies reveal that the substitution of functional group (s) at C-4 and C-2 positions plays a vital role in the activity of this series of compounds. It is concluded that compound 7 may act as a potential lead molecule to develop new drugs for the treatment of tyrosinase based disorders.
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical Sciences, University Karachi, Karachi-75270, Pakistan. hassaan2@super.net.pk
authors.forename: Khalid Mohammed
authors.initials: KM
authors.lastname: Khan
authors.forename: Uzma Rasool
authors.initials: UR
authors.lastname: Mughal
authors.forename: Mahmud Tareq Hassan
authors.initials: MT
authors.lastname: Khan
authors.lastname: Zia-Ullah
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Perveen
authors.forename: Muhammad Iqbal
authors.initials: MI
authors.lastname: Choudhary
mesh_terms: D020128:Inhibitory Concentration 50; D007980:Levodopa / Q000378:metabolism; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010081:Oxazolone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D010455:Peptides; D010081:Oxazolone; D007980:Levodopa; D014442:Monophenol Monooxygenase