Understanding human rhinovirus infections in terms of QSAR

AbstractThe human rhinoviruses (HRVs) are the single most important cause of common colds. The widespread nature of this affliction, the economic consequences, and the well-known impracticality of vaccine development due to the large number of HRV serotypes (>100) have justified the search for chemotherapeutic agents. The interest in the application of quantitative structure–activity relationships has steadily increased in recent decades and we hope it may be useful in the search for anti-HRV agents. In the present paper, we have discussed the inhibition of various six compound series against HRV-1A, -1B, -2, -9, -14, -21, -22, -25, -64, and -89 by the formulation of a total number of 14 QSAR. Hydrophobicity is found to be one of the most important determinants of activity. Parabolic correlation with the hydrophobic parameter (Eq. (7)) is an encouraging example, where the optimal hydrophobicity is well defined. We believe that this may be the predictive model to narrow the synthetic challenges in order to yield very specific HRV-2 inhibitors. On the basis of this model, we have predicted eleven compounds (I-1 to I-11) that may be the next synthetic target. The proposed molecules (I-1 to I-11) also fulfill the conditions of Lipinski's “rule of five”

Synthsis of hemin and porphyrin derivatives and their evaluation for anticancer activity

113-119N, Ethylaminoadenosine, histamine, 2-amino-2-thiazoline, 4-aminoantipyrine, sulphathiazole and a number of 3,4-diaryl-2-iminothiazolines are coupled with hemin to give bis coupled products 3a, 3b, 3c, 3d, 3e and 3f-m, respectively. Mono coupling of 2-amino-2-thiazoline with hemin gives isomeric mixture of mono coupled product 4. Deuteroporphyrin IX dicarboxylic acid is coupled with 2-amino-2-thiazoline to give bis coupled product 6 which on treatment with MnCl2,4H2O gives compound 7. Compounds 3a-m and 4 have been screened for anticancer activity against a small panel of six cancer cell lines consisting of prostate tumour (DU 145, PC3), colon carcinoma (HT29 or SW620), melanoma (SK-MEL-5, LOX), breast cancer (MCF 7 and adriamycin resistant MCF 7), CNS (U251) and ovarian cancer (IGROV1). Best GI50 (concentration which inhibits the cell growth by 50%), values are shown by 3f, 6.3μM (prostate tumour, cell line DU 145); 3f, 6.1 μM (colon tumor, cell line HT29); 4, 2.09 μM (colon tumor, cell line SW620); 3f, 2.2 μM (melanoma tumor, cell line LOX); 3i, 4.4μM (breast tumor, cell line MCF7/ADR); 3j, 2.68μM (ovarian tumor, cell line IGROV1) and 3g, 1.25μM (CNS tumor, cell line U 251) respectively

Novel peptidomimetic compounds containing redox active chalcogens and quinones as potential anticancer agents.

Many types of cancer cells are associated with a disturbed intracellular redox balance and oxidative stress (OS). Among the various agents employed to modulate the intracellular redox state of cells, certain redox catalysts containing quinone and chalcogen moieties have shown considerable promise. Passerini multicomponent reaction has been developed for the synthesis of agents combining two, three or even four redox centers in one molecule in a good yield. When incubated with cancer cells these agents inhibited cell proliferation and induced apoptotic cell death. Interestingly, some of these redox active compounds exhibited quite low toxicity with normal cells. The cause was obviously OS, which was reflected by significant decrease in reduced glutathione, subsequently cell cycle arrest and induction of apoptosis

Molecular basis of the interaction of novel tributyltin(IV) 2/4-[(E)-2-(aryl)-1-diazenyl] benzoates endowed with an improved cytotoxic pro!le: Synthesis, structure, biological ef!cacy and QSAR studies

A series of tributyltin(IV) complexes based on 2/4-[(E)-2-(aryl)-1-diazenyl]benzoate ligands was synthesized, wherein the position of the carboxylate and aryl substituents (methyl, tert-butyl and hydroxyl) varies. The complexes, Bu(3)SnL(1-4)H (1-4), have been structurally characterized by elemental analysis and IR, NMR ((1)H, (13)C, and (119)Sn) and (119)Sn Mossbauer spectroscopy. All have a tetrahedral geometry in solution and a trigonal bipyramidal geometry in the solid-state, except for Bu(3)SnL(4)H (4) that was ascertained to have tetrahedral coordination by X-ray crystallography. Cytotoxicity studies were carried out on human tumor cell lines A498 (renal cancer), EVSA-T (mammary cancer), H226 (non-small-cell lung cancer), IGROV (ovarian cancer), M19 MEL (melanoma), MCF-7 (mammary cancer) and WIDR (colon cancer). Compared to cisplatin, test compounds 1-4 had remarkably good activity, despite the presence of substantial steric bulk due to Sn-Bu ligands. The quantitative structure-activity relationship (QSAR) studies for the cytotoxicity of organotin(IV) benzoates, along with some reference drug molecules, is also discussed against a panel of human tumor cell lines. Molecular structures of the tributyltin(IV) complexes (1-4) were fully optimized using the PM6 semi-empirical method and docking studies performed with key enzymes associated with the propagation of cancer, namely ribonucleotide reductase, thymidylate synthase, thymidylate phosphorylase and topoisomerase II. The theoretical results are discussed in relation to the mechanistic role of the cytotoxic active test compounds (1-4). (C) 2010 Elsevier Inc. All rights reserved