In recent times, the novel concept of generating hybrid molecules by pharmacophoric hybridisation approach is fast becoming an alternative to other existing strategies of drug development. These hybrids also known as 'dual drugs' or 'double drugs' are especially found to be effective in overcoming drug resistance problems. Towards this end, a lot of effort has been put for generating 4-aminoquinoline based hybrid molecules as next generation antimalarial drugs effective in malarial chemotherapy. This short review deals about the recent advances carried in the field of 4-aminoquinoline based molecular hybrids as potential antimalarial agents. It also presents a brief and simplified story on the development of 4-aminoquinolines as a mainstay in malarial research programmes.
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http://dx.doi.org/10.2174/1568026614666140808125728 | DOI Listing |
Molecules
December 2024
Medicinal Chemistry Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India.
In response to the escalating crisis of antimicrobial resistance (AMR), there is an urgent need to research and develop novel antibiotics. This study presents the synthesis and assessment of innovative 4-aminoquinoline-benzohydrazide-based molecular hybrids bearing aryl aldehydes () and substituted isatin warheads (), characterized using multispectroscopic techniques with high purity confirmed by HRMS. The compounds were evaluated against a panel of clinically relevant antibacterial strains including the Gram-positive , , and and a Gram-negative bacterial strain.
View Article and Find Full Text PDFFuture Med Chem
December 2024
Department of Chemistry, Guru Nanak Dev University, Amritsar, India.
The aim of this study is to synthesize indolo[2,3-]quinoxaline-4-aminoquinoline-based hybrids and evaluate their effectiveness against chloroquine-susceptible (3D7) and resistant (W2) strains, with expected inhibition of chloroquine resistance transporter (CRT) and heme. The hybrids were synthesized and evaluated against both susceptible and resistant strains. Molecular docking and studies were conducted to assess the binding affinities for the CRT protein.
View Article and Find Full Text PDFPLoS Pathog
October 2024
Laboratory of Tropical Diseases-Prof. Dr. Luiz Jacintho da Silva, Department of Genetics, Evolution, Microbiology and Immunology, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil.
Artemisinin-based combination therapy (ACT) is the mainstay of effective treatment of Plasmodium falciparum malaria. However, the long-term utility of ACTs is imperiled by widespread partial artemisinin resistance in Southeast Asia and its recent emergence in parts of East Africa. This underscores the need to identify chemotypes with new modes of action (MoAs) to circumvent resistance to ACTs.
View Article and Find Full Text PDFNat Commun
September 2024
Department of Medicine, University of Vermont Larner College of Medicine, Room 202 Stafford Hall, 95 Carrigan Drive, Burlington, Vermont, USA.
J Med Chem
September 2024
International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), College of Pharmacy, Jinan University, #855 Xingye Avenue, Guangzhou 511400, China.
The biofilm formation of involves multiple complex regulatory pathways; thus, blocking a single pathway is unlikely to achieve the desired antibiofilm efficacy. Herein, a series of hybrids of 3-hydroxypyridin-4(1)-ones and long-chain 4-aminoquinolines were synthesized as biofilm inhibitors against based on a multipathway antibiofilm strategy. Comprehensive structure-activity relationship studies identified compound as the most valuable antagonist, which significantly inhibited biofilm formation (IC = 5.
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