Vasantha Pattabhi

C—H...O Hydrogen Bonds in β-sheets

A detailed analysis of the occurrence of the C-H...O hydrogen bonds in sheet regions of proteins has been presented. 11 unique protein structures with resolution 1.3 A containing beta-sheets show a widespread presence of C-H...O hydrogen bonds. These have average C(alpha).O, CH...O distances and a C(alpha)-H...O angle of 3.29, 2.38 A and 143 degrees, respectively. As in the case of N-H...O hydrogen bonds, parallel and antiparallel beta-sheet regions show the same hydrogen-bond geometry. An inverse correlation is observed between the hydrogen-bond geometries involving the C(alpha)(i)-H...O=C and the N(i+1)-H...O=C suggesting that C-H...O hydrogen bonds may act as an additional stabilizing factor. The propensity of different amino-acid residues to form such hydrogen bonds varies and shows a clear preference for valine and threonine. C-H...O hydrogen bonds involving side chains also occur extensively in beta-sheet regions.

A Review of the Hepatotoxic Plant Lantana camara

Lantana (Lantana camara Linn) is a noxious weed that grows in many tropical and subtropical parts of the world. Ingestion of lantana foliage by grazing animals causes cholestasis and hepatotoxicity. Both ruminants and nonruminant animals such as guinea pigs, rabbits, and female rats are susceptible to the hepatotoxic action of lantana toxins. The hepatotoxins are pentacyclic triterpenoids called lantadenes. Molecular structure of lantadenes has been determined. Green unripe fruits of the plant are toxic to humans. Lantana spp. exert allelopathic action on the neighboring vegetation. The allelochemicals have been identified as phenolics, with umbelliferone, methylcoumarin, and salicylic acid being the most phytotoxic. In addition to phenolics, a recent report indicates lantadene A and B as more potent allelochemicals. Management of lantana toxicosis in animals is achieved by drenching with activated charcoal and supportive therapy. Recent reports on the bilirubin clearance effect of Chinese herbal tea Yin Zhi Huang (decoction of the plant Yin Chin, Artemisia capillaries, and three other herbs) or its active ingredient 6,7-dimethylesculetin, in jaundice are very exciting and warrant investigations on its, possible, ameliorative effects in lantana intoxicated animals. Research is being conducted on new drug discovery based on natural products in different parts of the lantana plant.

Structure of naproxen, C14H14O3

An effective inhibitor of cyclo-oxygenase. Mr=230.25 , monoclinic, P21, a= 13.3150(10), b = 5.7765 (4), c= 7.8732 (4)A, fl= 93.88 (1) °, V= 604.2 (1)A 3, Z= 2, Din= 1.25 (2) (flotation), D~= 1.265 Mg m -3, 2(Mo Ka 1) = 0.70926/~, #(Mo Ka) = 0.095 mm -1, F(000) = 244, T= 296 K, final R(F) = 0.061 for 1037 observed reflections. The rotation of the carboxyl group with respect to the benezene ring, which seems to be connected with anti-inflammatory potential, is similar to the other two substituted propionic acids already reported. The benzene rings in the naphthyl group are inclined at an angle of 5.2 (2) °. Introduction. The title compound, an effective inhibitor of the cyclo-oxygenase responsible for biosynthesis of prostaglandins, was obtained from Dr Natarajan, Institute of Basic Medical Sciences, Madras. It exhibits anti-inflammatory, analgesic and antipyretic activity in man (Goodman & Gilman, 1980). The analysis of its structure was undertaken to help to establish the structure-activity relationship in propionic acid derivatives.

Molecular basis of chromium insulin interactions

The physiological role of chromium (III) in diabetes mellitus has been an area of inconclusive research for many years. It is of great interest to explore the interactions made by chromium (III) to get a better insight into their role in glucose metabolism. To understand the molecular basis of chromium action we have carried out spectroscopic and crystallographic investigations on the binding of Cr(III)-Salen with insulin, as Cr(III)-Salen is reported to result in the enhancement of insulin activity. The Cr(III)-insulin complex formation has been characterised at two pHs, viz., 3.5 and 9.0 using UV-Vis and fluorescence studies. The crystallographic analysis of Cr(III)-Salen soaked cubic insulin crystals, using anomalous difference Fourier method, revealed B21 Glu to be the binding site for chromium (III).

Structural basis for selective inhibition of COX-2 by nimesulide

Nimesulide 1 is a novel nonsteroidal antiinflammatory drug which inhibits the enzyme cyclooxygenase 2 (COX-2) more selectively than cyclooxygenase 1 (COX-1). Molecular modelling studies have been carried out on complexes of 1 with COX-1 and with mutants of COX-1 simulating COX-2. These indicate that the mutations I523V and S516A largely contribute to the selectivity. A comparative study with SC-558 2 has also been performed.

SYNTHESIS AND CHARACTERIZATION OF 1-AMINO-4-METHYLTHIO-2-NITRO-1,3-BUTADIENES

Treatment of 3-nitrothiophene with prim. and sec. amines, followed by S-methylation leads to (Z,Z)-1- amino-4-methylthio-2-nitro-1,3-butadienes (3). Oxidation of these with LTA yields a mixture of the 2-methylthio-4-nitropyrroles (6) and the acetoxylated butadienes (8).

Crystal structure of benzocaine—A local anaesthetic

The structure of the local anaesthetic benzocaine was solved by direct methods and refined to anR of 0·12 for 531 observed reflections. The packing of the molecule is stabilised by N−H … O hydrogen-bonds (2–97 Â). The alkyl chain attached to the benzene ring is intrans-trans conformation. The benzoic moiety shows a quinonoid character as found in some other local anaesthetics.

4-Hydroxy-2-methyl-N-(5-methyl-1,3-thiazol-2-yl)-2H-1,2-benzothiazine-3-carboxamide 1,1-Dioxide

The thiazine ring in the title compound, C14H13N3O4S2, adopts a half-chair conformation. The methyl group at N3 is axial to the thiazine ring due to the tetrahedral geometry of the N3 atom. The molecules are stabilized by intramolecular O—H⋯O and intermolecular N—H⋯O hydrogen bonds.

First and unexpected synthesis of macrocyclic cyclophane-based unusual α-amino acid derivatives by phosphazene base without high dilution conditions

First synthesis of a macrocylic cyclophane-based unusual alpha-amino acid derivative 11 by coupling of ethyl isocyanoacetate with 1,2-bis(4-bromomethylphenyl)ethane under phase-transfer catalysis (PTC) conditions. Phosphazene base such as 2-tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine (BEMP) is useful to improve the yield of cyclophane derivative without high dilution conditions.

Crystal structure at 1.63 A resolution of the native form of porcine beta-trypsin: revealing an acetate ion binding site and functional water network.

The active center of a serine protease is the catalytic triad composed of His-57, Ser-195 and Asp-102. The existing crystal structure data on serine proteases have not fully answered a number of fundamental questions relating to the catalytic activity of serine proteases. The new high resolution native porcine beta-trypsin (BPT) structure is aimed at extending the knowledge on the conformation of the active site and the ordered water structure within and around the active site. The crystal structure of BPT has been determined at 1.63 A resolution. An acetate ion bound at the active site of a trypsin molecule by both classical hydrogen bonds and C-HellipsisO hydrogen bonds has been identified for the first time. A large network of water molecules extending from the recognition amino acid Asp-184 to the entry of the active site has been observed in the BPT structure. A detailed comparison with inhibitor complexes and autolysates indicates that the sulfate ion and the acetate ion bind at the same site of the trypsin molecule. The Ser-195 Cbeta-Ogamma-His-57 Nepsilon angle in the catalytic triad of BPT is intermediate between the corresponding values of the complex and native structure due to acetate ion binding. The network of waters from the recognition amino acid to the active site entry is probably the first ever complete picture of functional waters around the active site. Structural comparisons show that the functional waters involved in the binding of small molecule inhibitors and protease inhibitors are distinctly different.