title: Monoamine Oxidase Inhibition and Molecular Modeling Studies of Piperidyl-thienyl and 2-Pyrazoline Derivatives of Chalcones.
abstract: A series of piperidyl-thienyl & 2-pyrazoline derivatives of quinolyl-thienyl chalcones were tested to observe the structural characteristics for the monoamine oxidase inhibitory (MAO) activity. In both these series, a diverse range of substituted thiophenes are used which enable the structure activity relationship. The compounds showed enhanced inhibition against MAO-A & B as compared to reference compounds. Compound 1c exhibited most potent MAO-A inhibition having IC50 value of 0.062 µM, while 1j showed excellent inhibitory potency against MAO-B having IC50 value of 0.088 µM. The present investigation demonstrated that among piperidyl-thienyl chalcones, almost all the compounds exhibit significant MAO-A inhibition, thus may have antidepressant activity. Whereas among the 2-pyrazoline derivatives of chal-cones, many compounds revealed MAOB inhibition and hence may be applied in the control of senile dementia. Molecular docking studies were carried out against human MAO-A and MAO-B to rationalize important binding site interactions.
authors.forename: Sumera
authors.initials: S
authors.lastname: Zaib
authors.forename: Syed Umar
authors.initials: SU
authors.lastname: Farooq Rizvi
authors.forename: Sana
authors.initials: S
authors.lastname: Aslam
authors.forename: Matloob
authors.initials: M
authors.lastname: Ahmad
authors.forename: Mariya
authors.initials: M
authors.lastname: Al-Rashida
authors.affiliation: Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan. jamshediqb@googlemail.com.
authors.forename: Jamshed
authors.initials: J
authors.lastname: Iqbal
mesh_terms: D000818:Animals; D001665:Binding Sites; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011817:Rabbits; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D047188:Chalcones; D008996:Monoamine Oxidase Inhibitors; D010880:Piperidines; D013844:Thiazoles