Medicinal chemistry updates on quinoline- and endoperoxide-based hybrids with potent antimalarial activity.

RSC Med Chem

Medicinal Chemistry Laboratory, Department of Biosciences, Jamia Millia Islamia Jamia Nagar New Delhi-110025 India +91 8750295095.

Published: January 2021

The resistance of conventional antimalarial drugs against the malarial parasite continues to pose a challenge to control the disease. The indiscriminate exploitation of the available antimalarials has resulted in increasing treatment failures, which urges on the search for novel lead molecules. Artemisinin-based combination therapy (ACT) is the current WHO-recommended first-line treatment for the majority of malaria cases. Hybrid molecules offer a newer strategy for the development of next-generation antimalarial drugs. These comprise molecules, each with an individual pharmacological activity, linked together into a single hybrid molecule. This approach has been utilized by several research groups to develop molecules with potent antimalarial activity. In this review, we provide an overview of the pivotal roles of quinoline- and endoperoxide-based hybrids as inhibitors of the life-cycle progression of . Based on the exhaustive literature reports, we have collated the structural and functional analyses of quinoline- and endoperoxide-based hybrid molecules that show potency equal to or greater than those of the individual compounds, offering an effective therapeutics option for clinical use.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132992PMC
http://dx.doi.org/10.1039/d0md00244eDOI Listing

Publication Analysis

Top Keywords

quinoline- endoperoxide-based
12
endoperoxide-based hybrids
8
potent antimalarial
8
antimalarial activity
8
antimalarial drugs
8
hybrid molecules
8
molecules
5
medicinal chemistry
4
chemistry updates
4
updates quinoline-
4

Similar Publications

Medicinal chemistry updates on quinoline- and endoperoxide-based hybrids with potent antimalarial activity.

RSC Med Chem

January 2021

Medicinal Chemistry Laboratory, Department of Biosciences, Jamia Millia Islamia Jamia Nagar New Delhi-110025 India +91 8750295095.

The resistance of conventional antimalarial drugs against the malarial parasite continues to pose a challenge to control the disease. The indiscriminate exploitation of the available antimalarials has resulted in increasing treatment failures, which urges on the search for novel lead molecules. Artemisinin-based combination therapy (ACT) is the current WHO-recommended first-line treatment for the majority of malaria cases.

View Article and Find Full Text PDF

Emergence and spread of Plasmodium falciparum resistant to artemisinin-based combination therapy has led to a situation of haste in the scientific and pharmaceutical communities. Sincere efforts are redirected towards finding alternative chemotherapeutic agents that are capable of combating multidrug-resistant parasite strains. Extensive research yielded the concept of "Chimeric Bitherapy (CB)" which involves the linking of two molecules with individual pharmacological activity and exhibit dual mode of action into a single hybrid molecule.

View Article and Find Full Text PDF

An endoperoxide-based hybrid approach to deliver falcipain inhibitors inside malaria parasites.

ChemMedChem

September 2013

iMed.UL and Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, Lisbon 1649-003, Portugal.

The emergence of artemisinin-resistant Plasmodium falciparum malaria in Southeast Asia has reinforced the urgent need to discover novel chemotherapeutic strategies to treat and control malaria. To address this problem, we prepared a set of dual-acting tetraoxane-based hybrid molecules designed to deliver a falcipain-2 (FP-2) inhibitor upon activation by iron(II) in the parasite digestive vacuole. These hybrids are active in the low nanomolar range against chloroquine-sensitive and chloroquine-resistant P.

View Article and Find Full Text PDF

Hybrid drugs for malaria.

Curr Pharm Des

November 2009

Panoz Institute, Trinity College Dublin, Ireland.

Malaria continues to devastate much of the tropics and sub-tropics in spite of the availability of a number of antimalarial drugs. Part of this problem is due to the disadvantages of the drugs in use, which include (depending on the drug) side effects, reduced efficacy due to resistance, and high cost. Multiple traditional and novel approaches to the discovery and design of new antimalarial agents are likely to be required to furnish the new drugs necessary for improved malaria control.

View Article and Find Full Text PDF

From mechanistic studies on artemisinin derivatives to new modular antimalarial drugs.

Acc Chem Res

March 2002

Laboratoire de Chimie de Coordination du CNRS, 205 route de Narbonne, 31077 Toulouse Cedex 4, France.

In the first part of this account, the antimalarial drug artemisinin is presented, and the current hypotheses on the mechanism of action of this endoperoxide-based drug are reviewed. The alkylating ability of artemisinin and synthetic analogues toward heme related to their antimalarial efficacy are underlined. Some possible ways for discovery of new drugs, especially the design of trioxaquines, new active molecules recently patented that have been prepared by covalent attachment of a trioxane residue having alkylating ability to a quinoline moiety known to easily penetrate within infected erythrocytes, are presented.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!