The PI3-kinase (PI3K) pathway regulates many cellular processes, especially cell metabolism, cell survival, and apoptosis. Phosphatidylinositol-3,4,5-trisphosphate (PIP3), the product of PI3K activity and a key signaling molecule, acts by recruiting pleckstrin-homology (PH) domain-containing proteins to cell membranes. Here, we describe a new structural class of nonphosphoinositide small molecule antagonists (PITenins, PITs) of PIP3-PH domain interactions (IC 50 ranges from 13.4 to 31 μM in PIP3/Akt PH domain binding assay). PITs inhibit interactions of a number of PIP3-binding PH domains, including those of Akt and PDK1, without affecting several PIP2-selective PH domains. As a result, PITs suppress the PI3K-PDK1-Akt pathway and trigger metabolic stress and apoptosis. A PIT-1 analog displayed significant antitumor activity in vivo, including inhibition of tumor growth and induction of apoptosis. Overall, our studies demonstrate the feasibility of developing specific small molecule antagonists of PIP3 signaling.PIP3 antagonist | anticancer

SummaryIncrease in invasive fungal infections over the past few years especially in immunocompromised patients prompted the search for new antifungal agents with improved efficacy. Current antifungal armoury includes very few effective drugs like Amphotericin B; new generation azoles, including voriconazole and posaconazole; echinocandins like caspofungin and micafungin to name a few. Azole class of antifungals which target the fungal cell membrane are the first choice of treatment for many years because of their effectiveness. As the fungal cell membrane is predominantly made up of sterols, glycerophospholipids and sphingolipids, the role of lipids in pathogenesis and target identification for improved therapeutics were largely pursued by researchers during the last few years. Present review focuses on cell membrane as an antifungal target with emphasis on membrane biogenesis, structure and function of cell membrane, cell membrane inhibitors, screening assays, recent advances and future prospects.

The production of a new class of glycolipid-metal nanoparticle conjugates, namely, sophorolipid reduced/capped silver nanoparticles is demonstrated for the first time, by unveiling the reducing and capping abilities of sophorolipid derived from oleic acid. It is also demonstrated that the sophorolipid capped Ag nanoparticles are highly potent antibacterial agents, against both Gram-positive and Gram-negative bacteria. The utilization of sophorolipid brings out several advantages, such as eliminating the necessity for exogenous reducing agent and imparting better stability to the silver nanoparticles as compared to their oleic acid capped analogues. These sophorolipid capped silver nanoparticles can be obtained as a stable powder that can be re-dispersed in water as desired.

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We report in situ synthesis of silver nanoparticles using biosurfactants called sophorolipids as reducing and capping agents. We further study the effect of temperature and the structure of sophorolipid on the size of silver nanoparticles obtained. The silver nanoparticles were characterized by UVvisible, transmission electron microscope (TEM) and light scattering (DLS) analysis techniques.