Toward Mycobacterium tuberculosis DXR inhibitor design: homology modeling and molecular dynamics simulations.

Mycobacterium tuberculosis 1-deoxy-D: -xylulose-5-phosphate reductoisomerase (MtDXR) is a potential target for antitubercular chemotherapy. In the absence of its crystallographic structure, our aim was to develop a structural model of MtDXR. This will allow us to gain early insight into the structure and function of the enzyme and its likely binding to ligands and cofactors and thus, facilitate structure-based inhibitor design.

Atypical presentation of renal cell carcinoma: a case report.

A case of Renal Cell Carcinoma (RCC) presenting to the Emergency Department with pyrexia and rigors is discussed.

Targeting the methyl erythritol phosphate (MEP) pathway for novel antimalarial, antibacterial and herbicidal drug discovery: inhibition of 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) enzyme.

The 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway for isoprenoid biosynthesis has come under increased scrutiny as a target for novel antimalarial, antibacterial and herbicidal agents. 1-Deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) is a key enzyme of the pathway that catalyzes the rearrangement and nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reduction of 1-deoxy-D-xylulose 5-phosphate (DXP) to MEP. The unique properties of DXR make it a remarkable and rational target for drug design.

p-Hydroxyphenylpyruvate dioxygenase is a herbicidal target site for beta-triketones from Leptospermum scoparium.

p-Hydroxyphenylpyruvate dioxygenase (HPPD) is a key enzyme in tyrosine catabolism and is the molecular target site of beta-triketone pharmacophores used to treat hypertyrosinemia in humans. In plants, HPPD is involved in the biosynthesis of prenyl quinones and tocopherols, and is the target site of beta-triketone herbicides. The beta-triketone-rich essential oil of manuka (Leptospermum scoparium), and its components leptospermone, grandiflorone and flavesone were tested for their activity in whole-plant bioassays and for their potency against HPPD.

A combined ligand-based and target-based drug design approach for G-protein coupled receptors: application to salvinorin A, a selective kappa opioid receptor agonist.

Combined ligand-based and target-based drug design approaches provide a synergistic advantage over either method individually. Therefore, we set out to develop a powerful virtual screening model to identify novel molecular scaffolds as potential leads for the human KOP (hKOP) receptor employing a combined approach. Utilizing a set of recently reported derivatives of salvinorin A, a structurally unique KOP receptor agonist, a pharmacophore model was developed that consisted of two hydrogen bond acceptor and three hydrophobic features.

Comparative protein modeling of 1-deoxy-D-xylulose-5-phosphate reductoisomerase enzyme from Plasmodium falciparum: a potential target for antimalarial drug discovery.

Plasmodium falciparum 1-deoxy-D-xylulose-5-phosphate reductoisomerase (Pf-DXR) is a potential target for antimalarial chemotherapy. The three-dimensional model (3D) of this enzyme was determined by means of comparative modeling through multiple alignment followed by intensive optimization, minimization, and validation. The resulting model demonstrates a reasonable topology as gauged from the Ramachandran plot and acceptable three-dimensional structure compatibility as assessed by the Profiles-3D score.

Pleomorphic lipoma of the tonsillar fossa--a case report.

Pleomorphic lipoma is a benign adipocytic tumor, commonly located in the shoulder and posterior neck region. The presence of bizarre, hyperchromatic stromal cells along with multinucleated giant cells often poses difficulty in diagnosis, especially when it arises at an unusual site like tonsillar fossa.

Inflammatory fibroid polyp of small intestine in a child.

Inflammatory fibroid polyps are rare lesions that are usually solitary and affect adults. We report an inflammatory fibroid polyp in a 7-year-old boy who presented with intestinal obstruction. He recovered after excision of the affected segment of ileum.

QSAR studies in substituted 1,2,3,4,6,7,12,12a-octa-hydropyrazino[2',1':6,1]pyrido[3,4-b]indoles--a potent class of neuroleptics.

A series of nineteen substituted 1,2,3,4,6,7,12,12a-octahydropyrazino[2',1':6,1]pyrido[3, 4-b]indoles analogues of neuroleptic drug, Centbutindole have been studied using quantitative structure-activity relationship analysis. The derived models display good fits to the experimental data (r>or=0.75) having good predictive power (r(cv)>or=0.