HIV-1 protease is an obligatory enzyme in the replication process of the HIV virus. The abundance of structural information on HIV-1PR has made the enzyme an attractive target for computer-aided drug design strategies. The daunting ability of the virus to rapidly generate resistant mutants suggests that there is an ongoing need for new HIV-1PR inhibitors with better efficacy profiles and reduced toxicity. In the present investigation, molecular modeling studies were performed on a series of 54 cyclic urea analogs with symmetric P2/P2' substituents. The binding modes of these inhibitors were determined by docking. The docking results also provided a reliable conformational superimposition scheme for the 3D-QSAR studies. To gain insight into the steric, electrostatic, hydrophobic and hydrogen-bonding properties of these molecules and their influence on the inhibitory activity, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed. Two different alignment schemes viz. receptor-based and atom-fit alignment, were used in this study to build the QSAR models. The derived 3D-QSAR models were found to be robust with statistically significant r(2) and r(2)(pred) values and have led to the identification of regions important for steric, hydrophobic and electronic interactions. The predictive ability of the models was assessed on a set of molecules that were not included in the training set. Superimposition of the 3D-contour maps generated from these models onto the active site of enzyme provided additional insight into the structural requirements of these inhibitors. The CoMFA and CoMSIA models were used to design some new inhibitors with improved binding affinity. Pharmacokinetic and toxicity predictions were also carried out for these molecules to gauge their ADME and safety profile. The computational results may open up new avenues for synthesis of potent HIV-1 protease inhibitors.

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16Water contamination is a global concern and its purification is essential to ensure a healthy life. 17The current approach to purify water is reduction of impurities to acceptable levels. One of the 18 ways in which this can be achieved is by use of water soluble synthetic polymers that are able to 19 extract organic contaminants, while polymers that are biodegradable can be used to extract toxic 20 metals from water. In this paper we present a blend of composite polymers that are able to 21 extract both these types of contaminants (organic and metallic) simultaneously by the principle of 22 adsorption at LCST. These composite polymers have been synthesized by grafting polymers such 23 as poly(N,N-diethylacrylamide), poly(N-isopropylacrylamide) and poly(N-vinylcaprolactum) on 24 to the natural polymer chitosan or its derivatives giving smart graft polymeric assemblies (GPA). 25One such graft polymer, GPA-2 exhibits excellent adsorption properties and is able to remove 26 metal ions such as cadmium, cobalt, copper, lead, iron as well as organic impurities like 27 chlorophenol and phthalic anhydride. Studies reveal that 6 mg/ml of the polymer GPA-2 is able to 28 effect a 100% removal of the two organic impurities -chlorophenol (50 ppm) and phthalic 29 anhydride (70 ppm) from water, while complete removal of the three heavy metal ions (Cu +2 , 30 Co+2 and Cd +2

Polymeric drug conjugates (PDCs) for cancer therapy have been a hot topic of research for the past three decades. Successful examples of PDC conjugates have demonstrated sustained drug release action with decreased systemic toxicity and enhanced tumor retention effect (EPR) via active as well as a passive targeting mechanisms. Therefore, the PDC approach has now become a keystone of the drug delivery system for cancer and other diseases. In recent years, several PDCs have successfully made up to the clinical trials. The approach aids targeted delivery of the anticancer drugs to the tumor site without disturbing the healthy cells. The selection of the over-expressed receptor and the receptor-ligand plays a vital role in designing the receptor-targeting PDC so that it is able to distinguish between the healthy cell and the tumor cell. Continuous efforts are being made in research and development towards active targeted PDC delivery system to revolutionize the treatment of cancer despite the controversy built due to hetereogeneity in tumor models. This review highlights the chemistry aspects involved in the preparation of PDCs that deal with novel molecular tumor targets and strategies used for development of targeted PDCs for delivering the drug payload via active or passive targeting. Further, it throws light on the challenges faced by targeted PDCs as novel drug delivery systems.