Structure-Activity Relationships of Natural and Semisynthetic Plecomacrolides Suggest Distinct Pathways for HIV-1 Immune Evasion and Vacuolar ATPase-Dependent Lysosomal Acidification.

The human immunodeficiency virus (HIV)-encoded accessory protein Nef enhances pathogenicity by reducing major histocompatibility complex I (MHC-I) cell surface expression, protecting HIV-infected cells from immune recognition. Nef-dependent downmodulation of MHC-I can be reversed by subnanomolar concentrations of concanamycin A (1), a well-known inhibitor of vacuolar ATPase, at concentrations below those that interfere with lysosomal acidification or degradation. We conducted a structure-activity relationship study that assessed 76 compounds for Nef inhibition, 24 and 72 h viability, and lysosomal neutralization in Nef-expressing primary T cells. This analysis demonstrated that the most potent compounds were natural concanamycins and their derivatives. Comparison against a set of new, semisynthetic concanamycins revealed that substituents at C-8 and acylation of C-9 significantly affected Nef potency, target cell viability, and lysosomal neutralization. These findings provide important progress toward understanding the mechanism of action of these compounds and the identification of an advanced lead anti-HIV Nef inhibitory compound.

Green Synthesis of Nanomaterials.

Nanotechnology is considered one of the paramount forefronts in science over the last decade. Its versatile implementations and fast-growing demand have paved the way for innovative measures for the synthesis of higher quality nanomaterials. In the early stages, traditional synthesis methods were utilized, and they relied on both carcinogenic chemicals and high energy input for production of nano-sized material. The pollution produced as a result of traditional synthesis methods induces a need for environmentally safer synthesis methods. As the downfalls of climate change become more abundant, the scientific community is persistently seeking solutions to combat the devastation caused by toxic production methods. Green methods for nanomaterial synthesis apply natural biological systems to nanomaterial production. The present review highlights the history of nanoparticle synthesis, starting with traditional methods and progressing towards green methods. Green synthesis is a method just as effective, if not more so, than traditional synthesis; it provides a sustainable approach to nanomaterial manufacturing by using naturally sourced starting materials and relying on low energy processes. The recent use of active molecules in natural biological systems such as bacteria, yeast, algae and fungi report successful results in the synthesis of various nanoparticle systems. Thus, the integration of green synthesis in scientific research and mass production provides a potential solution to the limitations of traditional synthesis methods.