ANALYSIS OF LIVER FUNCTION AND BIOCHEMICAL PARAMETERS OF FLUOROSIS AFFECTED RENAL FAILURE PATIENTS IN UDAYAGIRI MANDAL, NELLORE DISTRICT, A. P., INDIA

The alcoholic leaf extract of the three Indian medicinal plants Annona squamosa, Aegle marmelos and Citrus limon were screened for its antimicrobial activity using disc diffusion method. They were tested against four gram positive bacteria (Staphylococcus aureus, Staphylococcus epidermidis, Bacillus cereus, Bacillus subtilis), three gram negative bacteria (Escherichia coli, Pseudomonas aeruoginosa, Klebsiella pneumonia) and against three fungi (Aspergillus niger, Aspergillus fumigates,Candida albicans). It was observed that all the three alcoholic leaf extracts showed antibacterial and antifungal activity. The alcoholic leaf extract of Annona squamosa was found to be most active against S. aureus, B. cereus, K. pneumonia, A. niger and A.fumigates. The alcoholic leaf extract of Aegle marmelos was found to be active against B. subtilis, E. coli, P.aeuroginosa and C. albicans. The alcoholic leaf extract of Citrus limon was most active against S.epidermidis and E. coli. The susceptibility of the microorganisms to the extracts of these plants was compared with each other and with the standard antibiotics ciprofloxacin and ketoconozole. The antimicrobial activities of the three alcoholic leaf extracts are discussed according to their phytochemical components. It is concluded that these three Indian medicinal plants may serve as a valuable source of compounds with therapeutic potential.   &nbsp

Modeling of Molecular Interaction between Apoptin, BCR-Abl and CrkL - An Alternative Approach to Conventional Rational Drug Design

In this study we have calculated a 3D structure of apoptin and through modeling and docking approaches, we show its interaction with Bcr-Abl oncoprotein and its downstream signaling components, following which we confirm some of the newly-found interactions by biochemical methods. Bcr-Abl oncoprotein is aberrantly expressed in chronic myelogenous leukaemia (CML). It has several distinct functional domains in addition to the Abl kinase domain. The SH3 and SH2 domains cooperatively play important roles in autoinhibiting its kinase activity. Adapter molecules such as Grb2 and CrkL interact with proline-rich region and activate multiple Bcr-Abl downstream signaling pathways that contribute to growth and survival. Therefore, the oncogenic effect of Bcr-Abl could be inhibited by the interaction of small molecules with these domains. Apoptin is a viral protein with well-documented cancer-selective cytotoxicity. Apoptin attributes such as SH2-like sequence similarity with CrkL SH2 domain, unique SH3 domain binding sequence, presence of proline-rich segments, and its nuclear affinity render the molecule capable of interaction with Bcr-Abl. Despite almost two decades of research, the mode of apoptin’s action remains elusive because 3D structure of apoptin is unavailable. We performed in silico threedimensional modeling of apoptin, molecular docking experiments between apoptin model and the known structure of Bcr- Abl, and the 3D structures of SH2 domains of CrkL and Bcr-Abl. We also biochemically validated some of the interactions that were first predicted in silico. This structure-property relationship of apoptin may help in unlocking its cancer-selective toxic properties. Moreover, such models will guide us in developing of a new class of potent apoptin-like molecules with greater selectivity and potency