In this study, we have employed in silico methodology combining double pharmacophore based screening, molecular docking, and ADME/T filtering to identify dual binding site acetylcholinesterase inhibitors that can preferentially inhibit acetylcholinesterase and simultaneously inhibit the butyrylcholinesterase also but in the lesser extent than acetylcholinesterase. 3D-pharmacophore models of ACh...

Preface: Perceiving a pharmacophore is the most important first step towards understanding the interaction between a receptor and a ligand. In the early 1900s, Paul Ehrlich offered the first definition for a pharmacophore: "a molecular framework that carries (phoros) the essential features responsible for a drug’s (pharmacon) biological activity" (Ehrlich P: Dtsch Chem Ges 1909, 42:17). That de...

The parallel use of multiple pharmacophore models representing different pharmacological targets emerges as an in silico tool for compound activity profiling. This technology allows for the prediction of desired bioactivities together with potential adverse effects of a drug candidate. In thefield of ethnopharmacology,activity profiling can guide the rationalization of traditional drug uses and...

The crystal structure of the title compound, C(27)H(45)N(3), has been determined as part of our investigation into the hydro-phobic modification of amino-glycoside anti-biotics. The isopropyl group showed disorder for the tertiary carbon (equal occupancies), with high thermal motion for the peripheral atoms of the isopropyl and azide groups also apparent in the structure. The axial disposition ...

In the present study we have designed a new pharmacophore ‘Chalconesemicarbazone’ by pharmacophore hybridization approach of drug design. A series of novel ‘chalconylsemicarbazide’ derivatives was synthesized. The synthesized compounds were evaluated for their analgesic and anti-inflammatory activities. Most of the compounds were found to be more or comparable potent than the reference standard...

An arylazido ubiquinone derivative, 2,tdimethoxy5-methyl-6{10-[4-(azid0-2-nitroanilinopropionoxy)]decyl} -1,4-benzoquinone, restores about 60% of the electron transfer activity to ubiquinoneand phospholipid-depleted succinateor ubiquinol-cytochrome c reductases, compared to that restored by 2,3-dimethoxy5-methyl-6-(1O-bromodecyl)-1,4-benzoquinone. The restored activity is fully sensitive to ill...

We report the syntheses of antifungals containing the novel pharmacophores: oxaziridines, sulfonyloxaziridines, nitrones and nitronyl nitroxides. We hypothesized that multiple copies of the pharmacophore per molecule might be a prerequisite to enhance efficacy against the opportunistic pathogen, Pneumocystis carinii. Therefore structural optimization of the leads was based on this new “multival...

Focal adhesion kinase (FAK) is a tyrosine kinase that functions as a key orchestrator of signals leading to invasion and metastasis. In the current study, the multicomplex-based pharmacophore (MCBP)-guided method has been suggested to generate a comprehensive pharmacophore of FAK kinase based on seven crystal structures of FAK-inhibitor complexes. In this investigation, a hybrid protocol of vir...

Methione tRNA synthetase (MetRS) is an essential enzyme involved in protein biosynthesis in all living organisms and is a potential antibacterial target. In the current study, the structure-based pharmacophore (SBP)-guided method has been suggested to generate a comprehensive pharmacophore of MetRS based on fourteen crystal structures of MetRS-inhibitor complexes. In this investigation, a hybri...

Pancreatic cholesterol esterase (CEase) is a serine hydrolase involved in the hydrolysis of variety of lipids and transport of free cholesterol. In this study, pharmacophore hypotheses based on known inhibitors were generated using common feature pharmacophore generation protocol available in Discovery Studio program. The best pharmacophore model containing two hydrogen bond acceptor and three ...