Rationally designed small molecules inhibit malaria parasite at trophozoite stage to increase the median survival of malaria-infected mice

Identifying the Issue

• Spread of multi drug-resistance in malaria parasite
• Lack of novel therapy and effective drugs.

Objective of the Research

• Development of novel drug-like candidates with rapid kill kinetics against malaria parasite Plasmodium falciparum
• Non-haemolytic and non-toxic to animals

Who should read this?

Research community working in the Antiplasmodial drug development, medicinal chemists, and pharmaceutical industry

Solution

Development of nontoxic small molecules with high therapeutic effect and selectivity.

Key Features and Benefits

• Development of small molecules with rapid kill kinetics for Plasmodium falciparum trophozoite stage
• Non-toxic to mammalian cells and mice.
• Non-haemolytic drug-like molecules.
• Effective at low micromolar concentrations.

Impact

• Oral uptake of the drug for effective therapy.
• Minimizing the development of multi drug-resistance in malaria parasite when combined with other drugs.
• Effective against drug-resistant parasitic strains

Team

Siva Kumar Rokkam,^# Mamta Yadav,^# Mayank Joshi, Angshuman Roy Choudhury, Dinkar Sahal* and Nageswara Rao Golakoti*.

* Corresponding authors, ^#Equal contributions.

Title of paper: Synthesis, in vitro anti-plasmodial potency, in-silico-cum-SPR binding with inhibition of Pf Pyridoxal synthase and rapid parasiticidal action by 3,5-bis {(E) arylidene}-N-methyl-4-piperidones

Read Paper Here: https://doi.org/10.1039/D1NJ04604G

Fig. Antiplasmodial and antimalarial properties of DANMPs, a) Synthesis and characterization; b) interaction of the lead molecule with pyridoxal phosphate synthase; c) inhibition of parasitemia and cell cycle progression of PfMRA-1240 trophozoites in the presence of the lead molecule; d) best lead compound and its antiplasmodial potency.