Leishmaniasis, caused by the protozoan parasites of the genus Leishmania, is one of the most neglected diseases endemic in many continents posing enormous global health threats and therefore the discovery of new antileishmanial compounds is of utmost urgency. The antileishmanial activities of a library of sugar amino acid-based linear lipopeptide analogues were examined with the aim to identify potential drug candidates to treat visceral leishmaniasis. It was found that among the synthesized analogues, most of the permethylated compounds exhibited more activity in in vitro studies against intra-macrophagic amastigotes than the non-methylated analogues. SAR and NMR studies revealed that introduction of the N-methyl groups inhibited the formation of any turn structure in these molecules, which led to their improved activities.
Rapid population growth and urbanization have resulted in a multi-fold increase in water consumption over the last few decades, resulting in the generation of large amounts of sewage and sewage sludge that impose severe environmental burdens if not handled properly. Sludge management itself accounts for up to 50% of the total operating costs of wastewater treatment plants (WWTPs). Conventional sludge management practices such as incineration, landfilling, and ocean disposal have been deemed difficult in light of today’s stringent environmental legislation and compliance standards. As a result, progress has been made toward developing more sustainable approaches for sludge management. This study reviews recent advancements in sewage sludge management techniques that not only ensure the safe disposal of sewage sludge but also focus on utilizing the potential of sewage sludge as feedstock for energy and resource recovery. Energy could be recovered by subjecting the pre-treated sludge to controlled anaerobic digestion (AD) to produce biogas or by utilizing the lipid content of the sewage sludge through esterification or direct sludge pyrolysis to produce biodiesel/bio-oil. Heavy metals such as Ag, Au, Cu, Fe, Ga, Cr, and others, as well as nutrients such as N, P, K, Mg, S, and others, could also be recovered. If energy and resource recovery from sewage sludge is practiced on a global scale, it could significantly contribute to global greenhouse gas (GHG) emission reduction. This review discusses the commercially developed and still-under-research technologies for energy and other resource recovery of sewage sludge. Additionally, techniques, along with their limitations and potential measures to improve their yields, are also discussed.
HIV-1 reverse transcriptase (RT) is a key enzyme involved in the replication of the virus and is a potential target for therapeutic intervention following infection. Several drugs that inhibit the enzyme from acting have been discovered. These include nucleoside-analogue inhibitors such as AZT (zidovudine), ddI and ddC, and non-nucleoside inhibitors such as nevirapine and delavirdine. All of them, however have been found to be of limited clinical utility because the RT becomes rapidly resistant to them on account of point mutations in the enzyme. One way to partly overcome this limitation is to design an inhibitor that has interactions mainly with the backbone and the conserved residues of RT. Using a rational drug-design approach based on the high resolution X-ray crystal structure of the RT-nevirapine complex (1), and the specific design principles of peptides containing dehydro-Alanine (deltaAla) generated by our theoretical calculations, we present here the design of a peptide inhibitor of RT. Energy minimization and molecular modeling of the interaction of the designed pentapeptide with the nevirapine-binding site indicate that the inhibitor has 60% of its interactions with the conserved regions of RT as compared to 30% in the case of nevirapine, thus making it much less sensitive to mutations in the enzyme.
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