Mycobacterium tuberculosis chorismate mutase: A potential target for TB.

Mycobacterium tuberculosis chorismate mutase (MtbCM) catalyzes the rearrangement of chorismate to prephenate in the shikimate biosynthetic pathway to form the essential amino acids, phenylalanine and tyrosine. Two genes encoding chorismate mutase have been identified in Mtb. The secretory form,∗MtbCM (encoded by Rv1885c) is assumed to play a key role in pathogenesis of tuberculosis. Also, the inhibition of MtbCM may hinder the supply of nutrients to the organism. Indeed, the existence of chorismate mutase (CM) in bacteria, fungi and higher plants but not in human and low sequence homology among known CM makes it an interesting target for the discovery of anti-tubercular agents. The present article mainly focuses on the recent developments in the structure, function and inhibition of MtbCM. The understanding of various aspects of MtbCM as presented in the current article may facilitate the design and subsequent chemical synthesis of new inhibitors against ∗MtbCM, that could lead to the discovery and development of novel and potent anti-tubercular agents in future.

HIV-1 associated Topoisomerase IIß kinase: a potential pharmacological target for viral replication.

Viruses have been found to exhibit protein kinase activity associated with their purified viral particles. HIV-1 virus particles possess a novel 72 kD protein, Topoisomerase II beta kinase (Topo IIßKHIV) activity. The enzyme, isolated and purified from PEGprecipitated HIV-1 particles, is insensitive against a diverse set of known kinase inhibitors. The pyridine derivatives were found to be active against both Topo IIßKHIV activity and HIV-1 replication. For both kinase antagonism and anti-HIV-1 activity the Comparative Molecular Field Analysis (CoMFA) models were proposed. The CoMFA model was also evaluated independently with a set of test molecules for their anti-viral activity. The kinase inhibition and anti-viral activities for these inhibitors, tested in an in vitro kinase agree with the CoMFA model (cross-validated r2 (q2) value of 0.642 with six principal components), lower acceptable results are obtained with anti- HIV-1 activity (cross-validated r2 (q2) value of 0.358 with four principal components) and also correlate with relative solvation free energy calculations. The predictive power of the models was evaluated with 2 test molecules each and tends to lie within 1 log unit. An in cell validation of the model with a representative inhibitor, 2-methoxypyridine shows its ability to inhibit Topo IIß phosphorylation during acute HIV-1 infection. Close correlation of molecular fields of inhibitory domains of kinase and HIV-1 inhibitors suggests specificity of action of pyridine derivatives in affecting HIV-1 replication through inhibition of Kinase activity. These investigations suggest that Topo IIßKHIV is a potential target for an effective control of HIV-1 replication that would help in developing new anti-retroviral molecules.

Ethyl 4-(2-fur-yl)-2-oxochroman-3-carboxyl-ate.

The title compound, C(16)H(14)O(5), was prepared from the reaction of 3-carbethoxy-coumarin with furan in the presence of AlCl(3) as catalyst. In the crystal, inter-molecular C-H⋯O hydrogen-bonding inter-actions between four mol-ecules lead to a tetra-mer in the unit cell. The furan ring is anti-periplanar [C-C-C-O = 167.9 (13)°] and the ethoxy-carbonyl group is (-)anti-clinal [C-C-C-O = -128.6 (14)°] to the lactone ring.

Self-assembly of a fluorescent chiral zinc(II) complex that leads to supramolecular helices.

The chiral Zn(II) complex [ZnLCl(2)], 1 {L = 4-methyl-2,6-di[(S)-(+)-1-phenylethyliminomethyl] phenol}, self-assembles via C-H...Cl hydrogen bonding into supramolecular helices. Complex 1 exhibits emission in solution at room temperature in the visible range. Crystal data for 1: orthorhombic space group P2(1)2(1)2(1), a = 9.614(2) A, b = 13.825(3) A, c = 18.667(3) A, V = 2481.1(8) A(3), Z = 4.