Computer-aided Drug Design of Novel PLA(2) Inhibitor Candidates for Treatment of Snakebite

Phospholipases A(2) (PLA(2)) are enzymes commonly found in snake venoms from Viperidae and Elaphidae families, which are major components thereof. Many plants are used in traditional medicine its active agents against various effects induced by snakebite. This article presents the PLA(2) BthTX-I structure prediction based on homology modeling. In addition, we have performed virtual screening in a large database yielding a set of potential bioactive inhibitors. A flexible docking program was used to investigate the interactions between the receptor and the new ligands. We have performed molecular interaction fields (MIFs) calculations with the phospholipase model. Results confirm the important role of Lys49 for binding ligands and suggest three additional residues as well. We have proposed a theoretically nontoxic, drug-like, and potential novel BthTX-I inhibitor. These calculations have been used to guide the design of novel phospholipase inhibitors as potential lead compounds that may be optimized for future treatment of snakebite victims as well as other human diseases in which PLA(2) enzymes are involved.

Computer-aided drug design and ADMET predictions for identification and evaluation of novel potential farnesyltransferase inhibitors in cancer therapy

We have used various computational methodologies including molecular dynamics, density functional theory, virtual screening, ADMET predictions and molecular interaction field studies to design and analyze four novel potential inhibitors of farnesyltransferase (FTase). Evaluation of two proposals regarding their drug potential as well as lead compounds have indicated them as novel promising FTase inhibitors, with theoretically interesting pharmacotherapeutic profiles, when Compared to the very active and most cited FTase inhibitors that have activity data reported, which are launched drugs or compounds in clinical tests. One of our two proposals appears to be a more promising drug candidate and FTase inhibitor, but both derivative molecules indicate potentially very good pharmacotherapeutic profiles in comparison with Tipifarnib and Lonafarnib, two reference pharmaceuticals. Two other proposals have been selected with virtual screening approaches and investigated by LIS, which suggest novel and alternatives scaffolds to design future potential FTase inhibitors. Such compounds can be explored as promising molecules to initiate a research protocol in order to discover novel anticancer drug candidates targeting farnesyltransferase, in the fight against cancer. (C) 2009 Elsevier Inc. All rights reserved.

Traditional architecture in the Pacific

Architecture of the Pacific covers a region of more than third of the earth’s surface. The sparse Pacific population spreads over some 30 000 islands, which graduate in size from small atolls to the largest island, Australia, a continent. Pacific architecture can be studied as four cultural units: Micronesia, Polynesia, Melanesia, and Australasia (Australia and New Zealand). While many of the islands of Micronesia lie above the Equator, the remaining Pacific islands are in the southern hemisphere. With the exception of Australia, most of the islands have a warm and humid tropical climate with high rainfalls and lush vegetation. Some islands lie in the cyclonic and earthquake belts. Two distinct racial groups settled the region. The indigenous people, the Micronesians, Melanesians, Polynesians, Australian Aborigines and New Zealand Maoris, migrated from Asia thousands of years ago. The second group, the recent immigrants, were Europeans, who occupied the region during the last two centuries, and pockets of Asians brought in by colonial administrations as labourers during the early twentieth century.