Design and synthesis of potential antimicrobial agents

Chorismate mutase is one of the essential enzymes in the shikimate pathway and is key to the survival of the organism Mycobacterium tuberculosis. The x-ray crystal structure of this enzyme from Mycobacterium tuberculosis was manipulated to prepare an initial set of in silico protein models of the active site. Known inhibitors of the enzyme were docked into the active site using the flexible ligand / flexible active site side chains approach implemented in CAChe Worksystem (Fujitsu Ltd). The resulting complexes were refined by molecular dynamics studies in explicit water using Amber 9. This yielded a further set of protein models that were used for additional rounds of ligand docking. A binding hypothesis was established for the enzyme and this was used to screen a database of commercially available drug-like compounds. From these results new potential ligands were designed that fitted appropriately into the active site and matched the functional groups and binding motifs founds therein. Some of these compounds and close analogues were then synthesized and submitted for biological evaluation. As a separate part of this thesis, analogues of very active anti-tuberculosis pyridylcarboxamidrazone were also prepared. This was carried out by the addition and the deletion of the substitutions from the lead compound thereby preparing heteroaryl carboxamidrazone derivatives and related compounds. All these compounds were initially evaluated for biological activity against various gram positive organisms and then sent to the TAACF (USA) for screening against Mycobacterium tuberculosis. Some of the new compounds proved to be at least as potent as the original lead compound but less toxic.

Omnigen:providing electricity, food preparation, cold storage and pure water using a variety of local fuels

We describe a polygeneration system that can run on neat plant oils, such as Jatropha and Pongamia, or standard diesel fuel. A prototype has been constructed using a compression ignition engine of 9.9 kW shaft output. It consumes 3 L/h of fuel and will produce 40 kg/h of ice by means of an adsorption refrigerator powered from the engine jacket heat. Steaming of rice, deep and shallow frying, and other types of food preparation heated by the exhaust gas have been demonstrated. In addition, the feasibility of producing distilled water by means of multiple-effect distillation powered by the engine waste heat is shown. Overall plant efficiency and potential savings in greenhouse gas emissions are discussed. © 2012 Elsevier Ltd.