Association of XRCC1, XRCC3, and NAT2 polymorphisms with the risk of oral submucous fibrosis among eastern Indian population.

Background: Arecanut and smokeless tobacco usage is a major cause for oral submucous fibrosis (OSF) and its subsequent development to oral squamous cell carcinoma in South-east Asian population. Polymorphisms at N-acetyltransferase 2 locus, coding for an enzyme catalyzing acetylation of aromatic amines, might cause DNA adduct formation because of improper acetylation of these polyaromatic hydrocarbons. DNA repair enzymes remove these adduct to prevent malignancy.

In silico quest for putative drug targets in Helicobacter pylori HPAG1: molecular modeling of candidate enzymes from lipopolysaccharide biosynthesis pathway.

Aimed at identification and structural characterization of novel putative therapeutic targets in H. pylori, the etiological agent of numerous gastrointestinal diseases including peptic ulcer and gastric cancer, the present study comprised of three phases. First, through subtractive analysis of metabolic pathways of Helicobacter pylori HPAG1 and human, as documented in the KEGG database, 11 pathogen-specific pathways were identified.

Association of cholera toxin with Vibrio cholerae outer membrane vesicles which are internalized by human intestinal epithelial cells.

Cholera toxin (CT) is the major virulence factor of pathogenic Vibrio cholerae. The present study demonstrates that a fraction of CT is associated with the outer membrane vesicles (OMVs) released by V. cholerae.

Potent spermicidal effect of oleanolic acid 3-beta-D-glucuronide, an active principle isolated from the plant Sesbania sesban Merrill.

Background: The spermicidal activity of oleanolic acid 3-β-D-glucuronide (OAG), an active principle isolated from root extracts of Sesbania sesban, was evaluated.

Study Design: Under the Sander-Cramer test criteria, the sperm-immobilizing activity of OAG was studied using highly motile rat sperm. Sperm mortality and membrane integrity were assessed by supravital staining, hypo-osmotic swelling (HOS), transmission electron microscopy (TEM) and sperm membrane lipid peroxidation (LPO).

Pharmacophore models for GABA(A) modulators: implications in CNS drug discovery.

Importance Of The Field: GABA(A) ion channel is a validated drug target, implicated in the pathophysiology of various neurological and psychiatric disorders. Structural investigations on GABA(A) are currently precluded in the absence of experimentally resolved structure. Pharmacophore modeling circumvents such issues and proves to be a powerful and successful method in drug discovery.

Locked nucleosides based on oxabicyclo[3.2.1]octane and oxabicyclo[2.2.1]heptane skeletons.

Intramolecular nitrone cycloaddition (INC) reaction on a d-glucose derived substrate carrying an allyl group at C-1 and an enose-nitrone at C-5 or an aldehyde-nitrone at C-1 and vinyl group at C-4 furnished a tricyclo[6.2.1.

Probing the structure of Leishmania donovani chagasi DHFR-TS: comparative protein modeling and protein-ligand interaction studies.

Dihydrofolate reductase (DHFR) has been used successfully as a drug target in the area of anti-bacterial, anti-cancer and anti-malarial therapy. It also acts as a drug target for Leishmaniasis. Inhibition of DHFR leads to cell death through lack of thymine (nucleotide metabolism).

Molecular complexity of primary open angle glaucoma: current concepts.

Glaucoma is a group of heterogeneous optic neuropathies with complex genetic basis. Among the three principle subtypes of glaucoma, primary open angle glaucoma (POAG) occurs most frequently. Till date, 25 loci have been found to be linked to POAG.

Deciphering ligand dependent degree of binding site closure and its implication in inhibitor design: A modeling study on human adenosine kinase.

Protein flexibility plays a significant role in drug research due to its effect on accurate prediction of ligand binding mode and activity. Adenosine kinase (AK) represents a highly flexible binding site and is known to exhibit large conformational changes as a result of substrate or inhibitor binding. Here we propose a semi-open conformation for ligand binding in human AK, in addition to the known closed and open forms.

Combinatorial library enumeration and lead hopping using comparative interaction fingerprint analysis and classical 2D QSAR methods for seeking novel GABA(A) alpha(3) modulators.

Selective modulators of GABA(A) alpha(3) (gamma amino butyric acid alpha(3)) receptor are known to alleviate the side effects associated with nonspecific modulators. A follow up study was undertaken on a series of functionally selective phthalazines with an ideological credo of identifying more potent isofunctional chemotypes. A bioisosteric database enumerated using the combichem approach endorsed mining in a lead-like chemical space.

Hybrid structure-based virtual screening protocol for the identification of novel BACE1 inhibitors.

BACE1, also called beta-secretase or memapsin 2, is an extensively studied aspartic protease, involved in etiopathogenesis and progression of Alzheimer's disease (AD). We report herein a modified structure-based virtual screening protocol that augments the lead identification process against BACE1 during virtual screening endeavors. A hybrid structure-based virtual screening protocol that incorporates elements from both ligand-based and structure-based techniques was used for the identification of prospective small molecule inhibitors.