Isolation and characterization of blood-stage persisters by improved selection protocols using dihydroartemisinin alone.

Artemisinin-based combination therapies (ACTs) are vital for malaria treatment, but these are threatened by blood-stage persisters-dormant forms of parasites that can survive drug exposure and cause recrudescent infections. Here, we present improved protocols for efficient preparation of pure persister populations without the need for magnetically activated columns, sorbitol exposure, or prolonged manipulations. Our protocols transformed actively replicating parasites into persister populations by exposing mixed blood-stage parasites to three or four consecutive daily 6 h pulses of 700 nM or 200 nM dihydroartemisinin (DHA).

Diversity-oriented synthesis derived indole based spiro and fused small molecules kills artemisinin-resistant Plasmodium falciparum.

Background: Despite numerous efforts to eradicate the disease, malaria continues to remain one of the most dangerous infectious diseases plaguing the world. In the absence of any effective vaccines and with emerging drug resistance in the parasite against the majority of anti-malarial drugs, the search for new drugs is urgently needed for effective malaria treatment.

Methods: The goal of the present study was to examine the compound library, based on indoles generated through diversity-oriented synthesis belonging to four different architecture, i.

Inhibition of PfMYST Histone Acetyltransferase Activity Blocks Plasmodium falciparum Growth and Survival.

One of the major barriers in the prevention and control of malaria programs worldwide is the growing emergence of multidrug resistance in parasites, and this necessitates continued efforts to discover and develop effective drug molecules targeting novel proteins essential for parasite survival. In recent years, epigenetic regulators have evolved as an attractive drug target option owing to their crucial role in survival and development of at different stages of its life cycle. PfMYST, a histone acetyltransferase protein, is known to regulate key cellular processes, such as cell cycle progression, DNA damage repair, and antigenic variation, that facilitate parasite growth, adaptation, and survival inside its host.

Plasmodium falciparum RUVBL3 protein: a novel DNA modifying enzyme and an interacting partner of essential HAT protein MYST.

RUVBLs constitute a conserved group of ATPase proteins that play significant role in a variety of cellular processes including transcriptional regulation, cell cycle and DNA damage repair. Three RUVBL homologues, namely, PfRUVBL1, PfRUVBL2 and PfRUVBL3 have been identified in P. falciparum, unlike its eukaryotic counterparts, which have two RUVBL proteins (RUVBL1 & RUVBL2).

Pharmacological approach to increasing the retention of radiation-induced γ-H2AX foci using phosphatase inhibitors: significance in radiation biodosimetry.

In a scenario of accidental mass radiation exposure transportation and analysis of samples may take some time, resulting in loss of biomarker information over this period. The present study aims to use phosphatase inhibitors for longer retention of focal signals to adopt γ-H2AX as a biodosimetric biomarker for the management of early triage. Peripheral blood lymphocytes isolated from healthy individuals were irradiated in vitro with x-rays and γ-H2AX foci were analysed using fluorescent microscopy and flow cytometric methods.

Pharmacological approach to increase the retention of radiation induced gamma-H2AX foci using phosphatase inhibitors: significance in radiation biodosimetry.

In a scenario of accidental mass radiation exposure, transportation and analyzing samples may take its time resulting in loss of biomarker information over this period. The present study aims to use phosphatases inhibitors for longer retention of foci signals to adopt γ-H2AX as a biodosimetric biomarker for the management of early triage. Peripheral blood lymphocytes isolated from healthy individuals irradiated in vitro with X-rays, and γ-H2AX analysed using fluorescent microscopy and flow cytometric methods.