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...

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 ...

One pharmacophore model and three quantitative structure-activity relationship models were developed on a series of benzimidazole and imidazole inhibitors of histone deacetylase 2. The goodness of hit score value of the best pharmacophore model was 0.756, which indicated that it is reliable to be used for virtual screening. The built pharmacophore model was used to search the NCI database. The ...

Chemical features based 3D pharmacophore models were developed for HSP90 based on the known inhibitors using Discovery Studio V2.1. An optimal pharmacophore model was brought forth and validated using a decoy set, external test set and Fischer's randomization method. The best five features pharmacophore model, Hypo1, includes two hydrogen bond acceptors, three hydrophobic features, which has th...

The ligand binding determinants for the angiotensin II type 1 receptor (AT1R), a G protein-coupled receptor (GPCR), have been characterized by means of computer simulations. As a first step, a pharmacophore model of various known AT1R ligands exhibiting a wide range of binding affinities was generated. Second, a structural model of AT1R was built making use of the growing set of crystal structu...

The sodium-dependent organic anion transporter SOAT specifically transports sulfated steroid hormones and is supposed to play a role in testicular steroid regulation and male fertility. The present study aimed to identify novel specific SOAT inhibitors for further in vitro and in vivo studies on SOAT function. More than 100 compounds of different molecular structures were screened for inhibitio...

The HIV-1causes life-threatening infection by establishing essential biochemical interactions via its IN protein with human host LEDGF/p75 protein. The crystal structure availability of LEDEF–HIV-IN complex provide essential roadmap for designing small drug-like molecule to perturb pathogen-host proteins interaction. We adopted the in-silico drug discovery approaches and scanned the TIMBAL data...