4D quantitative structure-activity relationship (QSAR) and 3D pharmacophore models were built and investigated for cytotoxicity using a training set of 25 lamellarins against human hormone dependent T47D breast cancer cells. Receptor-independent (RI) 4D QSAR models were first constructed from the exploration of eight possible receptor-binding alignments for the entire training set. Since the tr...

In the present study we have investigated whether pharmacophore models may account for the activity and selectivity of the known cyclooxygenase-2 (COX-2) selective inhibitors of the phenylsulfonyl tricyclic series, i.e., Celecoxib (1) and Rofecoxib (3), and whether transferring this structural information onto the frame of a nonsteroidal antiinflammatory drug (NSAID), known to tightly bind the ...

Gamma-secretase is a trans-membrane aspartyl protease that consists of four subunits, namely Anterior Pharynx Defective Phenotype (APH-1), Presenilin (PSEN), Nicastrin (Nct) and Presenilin 2 Enhancer (PEN2). Presenilin is identified as the catalytic core of gamma-secretase with the two aspartyl residues at the catalytic site. Gamma-secretase is involved in the ultimate step in the processing of...

The pregnane X receptor (PXR) is involved in transcriptional regulation of multiple cytochromes P450 and multidrug resistance-associated protein (MDR1), which encodes for the drug transporter P-glycoprotein. Crystal structure analyses suggest that the ligand binding domain is highly hydrophobic and flexible, allowing molecules of differing sizes to bind in multiple orientations. Using literatur...

Allosteric inhibition of protein tyrosine phosphatase 1B (PTP1B), has paved a new path to design specific inhibitors for PTP1B, which is an important drug target for the treatment of type II diabetes and obesity. The PTP1B1-282-allosteric inhibitor complex crystal structure lacks alpha7 (287-298) and moreover there is no available 3D structure of PTP1B1-298 in open form. As the interaction betw...

The enzyme β-1,3-glucan synthase, which catalyzes the synthesis of β-1,3-glucan, an essential and unique structural component of the fungal cell wall, has been considered as a promising target for the development of less toxic anti-fungal agents. In this study, a robust pharmacophore model was developed and structure activity relationship analysis of 42 pyridazinone derivatives as β-1,3-glucan ...

Computational tools have greatly expedited the pharmaceutical drug design process in recent years. One common task in this process is the search of a large library for small molecules that can achieve both a low-energy conformation and a prescribed pharmacophore. The pharmacophore expresses constraints on the 3D structure of the molecule by specifying relative atom positions that should be main...

Hydrogen sulfide (H2S) has been regarded as the third gaseous transmitter. Based on the mechanism of chemoselective azido reduction and self-immolation, five fluorescence resonance energy transfer (FRET) probes for the detection of H2S were designed and synthesized. The effect of functional substitution of the self-immolative moiety on azido reduction and quinone-methide rearrangement were inve...

Thrombin, an important factor of clotting system, take part in a variety of physiological actions, such as blood clotting, anticoagulation, thrombosis and fibrinolysis. Inhibiting thrombin is a pivotal and effective step for the prophylaxis of venous and arterial thrombosis, as well as prevent myocardial infarction for high-risk patients. In this study, a three dimensional pharmacophore model w...

The present work delineates the combinatorial approach of firstly, creation of a centralized data-set comprising signalling proteins identified on the basis of altered expression, such as over-expression or repression of a set of signalling protein(s) leading to the cause of the disease, which is based on published reports screened through Pubmed and secondly, in the in silico creation of novel...