Synthesis of Novel Ciprofloxacin-Based Hybrid Molecules toward Potent Antimalarial Activity

Srikanta Dana; Praveesh Valissery; Sharvan Kumar; Sumiran Kumar Gurung; Neelima Mondal; Suman Kumar Dhar; Pritam Mukhopadhyay

doi:10.1021/acsmedchemlett.0c00196

Synthesis of Novel Ciprofloxacin-Based Hybrid Molecules toward Potent Antimalarial Activity

ACS Med Chem Lett. 2020 Jun 4;11(7):1450-1456. doi: 10.1021/acsmedchemlett.0c00196. eCollection 2020 Jul 9.

Authors

Srikanta Dana^{1

2}, Praveesh Valissery², Sharvan Kumar¹, Sumiran Kumar Gurung², Neelima Mondal², Suman Kumar Dhar², Pritam Mukhopadhyay¹

Affiliations

¹ Supramolecular and Material Chemistry Lab, School of Physical Sciences, Jawaharlal Nehru University, New Delhi - 110067, India.
² Special Center for Molecular Medicine and School of Life Sciences, Jawaharlal Nehru University, New Delhi - 110067, India.

Abstract

Antimalarial drug resistance is a serious obstacle in the persistent quest to eradicate malaria. There is a need for potent chemical agents that are able to act on drug-resistant Plasmodium falciparum populations at reasonable concentrations without any related toxicity to the host. By rational drug design, we envisaged to address this issue by generating a novel hybrid drug possessing two pharmacophores that can act on two unique and independent targets within the cell. We synthesized a new class of ciprofloxacin-based hybrid molecules, which have been integrated with acridine, quinolone, sulphonamide, and cinnamoyl pharmacophores (1-4). We realized a potent chloroquinolone-ciprofloxacin-based antimalarial hybrid (2, CQ-CFX) whose mechanism of action is unlike that of its parent molecules indicating a unique biological target. CQ-CFX is not only potent against CQ-resistant and susceptible strains of Plasmodium falciparum at low nanomolar concentrations (IC₅₀ values are 63.17 ± 1.2 nM and 25.52 ± 4.45 nM, respectively) but is also not toxic to mammalian and bacterial systems up to 20 μM and 1 μM, respectively.