AbstractBackgroundThe global incidences of leishmaniasis are increasing due to changing environmental conditions and growing poverty. Leishmaniasis, caused by the Leishmania parasite, presents itself in six different clinical forms, the cutaneous and the visceral diseases being the most prevalent. While the cutaneous form causes disfigurement, the visceral form could be fatal if not treated. With no available vaccines combined with serious side effects of current medications and emerging drug resistance, it is crucial to discover new drugs whether as novel compounds or as repurposed existing pharmaceuticals. In the realm of drug development, mitochondria are recognized as important pharmacological targets due to their critical role in energy control, which, when disrupted, leads to irreversible cell damage. Certain plant-based compounds able to target the parasite mitochondrion, have been studied for their potential anti-leishmanial effects.Search resultsThese compounds have shown promising effects in eliminating the Leishmania parasite. Artemisinin and chloroquine, two anti-malarial drugs that target mitochondria, exert strong anti-leishmanial effectiveness in both in vitro cultures and in vivo animal models. Quinolones, coumarins and quercetin are other compounds with leishmanicidal properties, which disrupt mitochondrial activity to effectively eliminate parasites in animal models of the disease and could be considered as potential drugs.ConclusionsTherefore, plant-based compounds hold promise as potential candidates for anti-leishmanial drug development.

01 Dec 2024·Biochemical and Biophysical Research Communications

Cholesterol-driven modulation of membrane-membrane interactions by an antimicrobial peptide, NK-2, in phospholipid vesicles

Article

Author: Chattopadhyay, Krishnananda ; Jain, Rajeev ; Karmakar, Sanat ; Das, Surajit ; Banerjee, Kalyan Kumar

Antimicrobial peptides (AMPs) are essential components of the innate immune system, demonstrating their antimicrobial effects primarily through the creation of transmembrane pores that result in membrane disruption. Cholesterol within the membrane can significantly affect the interaction between AMPs and the membrane, as it is known to alter both the permeability and elastic properties of the membrane. In this study, we have investigated the influence of cholesterol on the interaction of the AMP, NK-2 with phospholipid vesicles. We prepared giant unilamellar vesicles (GUVs) composed of DOPC-DOPG and Egg PC, varying the cholesterol concentrations, and analyzed them using phase contrast microscopy. The aggregation of vesicles is evident in the phase contrast microscopy observations of GUVs. The aggregation of GUVs with cholesterol ultimately leads to a collapse state, a condition not typically seen in GUVs lacking cholesterol. Furthermore, the aggregation kinetics were determined from the analysis of phase contrast micrographs. This biophysical investigation offers valuable insights into how cholesterol affects the interactions between membranes induced by antimicrobial peptides.

22 Nov 2024·Organic Letters

Synergistic [4 + 1] Spiroannulation and Selective Ring-Opening Strategy toward γ-Spirolactams

Article

Author: Deb, Indubhusan ; Purkait, Anisha ; Naskar, Koushik ; Roy, Shantonu ; Mondal, Imtiaj

A unique and propitious [4 + 1] spiroannulation of 2-aryl-4H-benzo[d][1,3]oxazine with maleimide has been delineated, furnishing diversely embellished γ-spirolactams featuring pendant benzyl alcohol via Rh(III)-catalyzed consecutive ring closing/ring opening followed by regioselective cleavage of the C4-O bond of 1,3-benzoxazine promoted by an in situ generated water maneuver constructing new C-C, C-N, and C-O bonds at a go. A detailed mechanistic study, including a thorough analysis of the incorporation of an extra oxygen source, has been showcased to make this strategy for structurally orchestrated isoindoline-1-one spirosuccinimides.

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