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Chemical Biology & Drug Design Aug 2021The activities of marine alkaloids are manifested in antifungus and antimalaria. The optimization process, chemical synthesis, antimalarial activity, and antibacterial... (Review)
Review
The activities of marine alkaloids are manifested in antifungus and antimalaria. The optimization process, chemical synthesis, antimalarial activity, and antibacterial activity of various compounds were discussed.
Topics: Alkaloids; Animals; Anti-Bacterial Agents; Antimalarials; Gram-Negative Bacteria; Gram-Positive Bacteria; Plasmodium falciparum; Porifera; Structure-Activity Relationship
PubMed: 34008345
DOI: 10.1111/cbdd.13892 -
Expert Opinion on Drug Discovery Jun 2020The unique physicochemical properties and chemical diversity of organofluorine compounds have remarkably contributed for their wide utility in the area of... (Review)
Review
INTRODUCTION
The unique physicochemical properties and chemical diversity of organofluorine compounds have remarkably contributed for their wide utility in the area of pharmaceuticals, materials and agrochemicals. The noteworthy characteristics of fluorine include high electron affinity, lipophilicity and bioavailability, extending the half-life of the drugs. The incorporation of fluorine substituents, particularly trifluoromethyl groups, into organic molecules has led to their high potency against various diseases, including malaria. Hence, organofluorinated molecules offer valuable avenues for the design of new drug candidates against malaria.
AREAS COVERED
In this review, the authors discuss the importance of fluorine substituents present in the chemical compounds, and their potential applications for antimalarial drug discovery.
EXPERT OPINION
Fluorinated molecules represent a reliable strategy to develop new antimalarial drugs. Fluorine or fluorinated groups have been identified as a promising precursor, and their presence in approximately twenty-five percent of approved drugs is notable. Selective fluorination of chemical entities has the potential to be applied not only to improve the activity profile against the malaria parasite, but could be extrapolated for favorable pharmacological applications. Hazardous reagents such as HF, F and SF used for fluorination, are not considered as safe, and therefore, this process remains challenging, particularly for the pharmaceutical industry.
Topics: Animals; Antimalarials; Drug Design; Drug Discovery; Fluorine; Halogenation; Humans; Malaria
PubMed: 32202162
DOI: 10.1080/17460441.2020.1740203 -
Journal of Complementary & Integrative... Sep 2019Malaria, caused mainly by Plasmodium falciparum among other Plasmodium species, is one of the main causes of death from parasitic diseases. Malaria is still a health... (Review)
Review
Malaria, caused mainly by Plasmodium falciparum among other Plasmodium species, is one of the main causes of death from parasitic diseases. Malaria is still a health problem mainly because of the cost of effective antimalarial drugs and the growing parasite resistance to conventional antimalarial drugs, making a great proportion of the people in malaria endemic countries dependent on plants for its treatment. Corollary, a large number of the rural populations consume antimalarial herbal preparations in large or excessive quantities despite the fact that it has been reported that some of them could cause male-factor infertility, a growing global health concern. Few studies have compiled information on the scientifically validated male-factor antifertility effects of these antimalarial plant remedies. The aim of this review therefore is to compile information on commonly used antimalarial plant remedies that have been experimentally validated as having male-factor antifertility effects. Thus, antimalarial plant remedies with experimentally confirmed male-factor antifertility potentials and compounds isolated from them are identified and discussed. The male-factor antifertility effects of these plants include reduction of sperm quality, regulation of reproductive hormone levels and induction of lipid peroxidation. Indiscriminate use of such antimalarial plants is discouraged when male contraception is not desired.
Topics: Animals; Antimalarials; Humans; Infertility, Male; Male; Plant Extracts; Plants, Medicinal
PubMed: 31527295
DOI: 10.1515/jcim-2018-0214 -
Mini Reviews in Medicinal Chemistry 2021Malaria, a devastating infectious parasitic disease, has been recognized by the World Health Organization (WHO) as a major public health problem worldwide. It is one of... (Review)
Review
INTRODUCTION
Malaria, a devastating infectious parasitic disease, has been recognized by the World Health Organization (WHO) as a major public health problem worldwide. It is one of the leading causes of morbidity and mortality in developing countries. There are a number of antimalarial drugs available in the market to combat this deadly disease. The situation is further worsened due to the emergence of resistant strains of Plasmodium falciparum, which warrants the search for novel antimalarial drugs capable of acting at multiple targets to expand the current antimalarial drug arsenal for better therapeutic outcome.
OBJECTIVES
This review aimed to provide the reader with the recent advances and progress made in the development of chemotherapeutic agents for malaria.
METHODS
Literature review data on the chemistry and antimalarial activity of natural and synthetic heterocyclic compounds published in the last ten years were compiled by referring to various peerreviewed journal websites and medical search engines.
RESULTS AND DISCUSSION
This review covers the recent advances and progress made in the treatment strategies, patent granted, synthetic approaches, mechanism of action with more emphasis on a Structure- activity Relationship (SAR) of potential chemotherapeutic agents as antimalarial agents which could pave the way for the development of more effective and potent antimalarial agents. This review might interest fellow researchers working on the development of novel antimalarial drug candidates with better therapeutic index.
CONCLUSION
Based on the literature covered in the current review article and seeing the recent trends, authors are of the opinion that the multi-target conjugated hybrid approach is the best strategy to discover and develop effective antimalarial agents.
Topics: Animals; Antimalarials; Drug Discovery; Humans; Malaria; Structure-Activity Relationship
PubMed: 33349215
DOI: 10.2174/1389557521666201221161750 -
Current Drug Discovery Technologies 2015Wiping out malaria is now the global concern as about three billion people are at risk of malaria infection globally. Despite of extensive research in the field of... (Review)
Review
Wiping out malaria is now the global concern as about three billion people are at risk of malaria infection globally. Despite of extensive research in the field of vaccine development for malaria, till now, no effective vaccine is available for use and hence only antimalarial drugs remain our best hope for both treatment and prevention of malaria. However, emergence and spread of drug resistance has been a major obstacle for the success of malaria elimination globally. This review will summarize the information related to antimalarial drugs, drug development strategies, drug delivery through nanoparticles, few current issues like adverse side effects of most antimalarial drugs, non availability of drugs in the market and use of fake/poor quality drugs that are hurdles to malaria control. As we don't have any other option in the present scenario, we have to take care of the existing tools and make them available to almost all malaria affected area.
Topics: Animals; Antimalarials; Disease Resistance; Drug Discovery; Humans; Malaria; Nanoparticles
PubMed: 26343059
DOI: 10.2174/1570163812666150907100019 -
Acta Tropica Dec 2015Although the burden of malaria is decreasing, parasite resistance to current antimalarial drugs and resistance to insecticides by vector mosquitoes threaten the... (Review)
Review
Although the burden of malaria is decreasing, parasite resistance to current antimalarial drugs and resistance to insecticides by vector mosquitoes threaten the prospects of malaria elimination in endemic areas. Corollary, there is a scientific departure to discover new antimalarial agents from nature. Because the two antimalarial drugs quinine and artemisinin were discovered through improved understanding of the indigenous knowledge of plants, bioprospecting Sub-Saharan Africa's enormous plant biodiversity may be a source of new and better drugs to treat malaria. This review analyses the medicinal plants used to manage malaria in Sub-Saharan Africa. Chemical compounds with antiplasmodial activity are described. In the Sub-Saharan African countries cited in this review, hundreds of plants are used as antimalarial remedies. While the number of plant species is not exhaustive, plants used in more than one country probably indicate better antimalarial efficacy and safety. The antiplasmodial data suggest an opportunity for inventing new antimalarial drugs from Sub-Saharan-African flora.
Topics: Africa South of the Sahara; Antimalarials; Malaria; Phytotherapy; Plants, Medicinal; Plasmodium
PubMed: 26297798
DOI: 10.1016/j.actatropica.2015.08.009 -
Current Protein & Peptide Science 2016Malaria, a deadly infectious parasitic disease, is a major issue of public health in the world today and already produces serious economic constraints in the endemic... (Review)
Review
Malaria, a deadly infectious parasitic disease, is a major issue of public health in the world today and already produces serious economic constraints in the endemic countries. Most of the malarial infections and deaths are due to Plasmodium falciparum and Plasmodium vivax species. The recent emergence of resistance necessitates the search for new antimalarial drugs, which overcome the resistance and act through new mechanisms. Although much effort has been directed towards the discovery of novel antimalarial drugs. 4-anilino quinolone triazines as potent antimalarial agents, their in silico modelling and bioevaluation as Plasmodium falciparum transketolase and β-hematin inhibitors has been reported. This review is primarily focused on the drug discovery of the recent advances in the development of antimalarial agents and their mechanism of action.
Topics: Animals; Antimalarials; Drug Discovery; Humans; Plasmodium falciparum
PubMed: 26796302
DOI: 10.2174/1389203717999160226180543 -
British Journal of Pharmacology Aug 2023Antimalarial drug discovery has until recently been driven by high-throughput phenotypic cellular screening, allowing millions of compounds to be assayed and delivering... (Review)
Review
Antimalarial drug discovery has until recently been driven by high-throughput phenotypic cellular screening, allowing millions of compounds to be assayed and delivering clinical drug candidates. In this review, we will focus on target-based approaches, describing recent advances in our understanding of druggable targets in the malaria parasite. Targeting multiple stages of the Plasmodium lifecycle, rather than just the clinically symptomatic asexual blood stage, has become a requirement for new antimalarial medicines, and we link pharmacological data clearly to the parasite stages to which it applies. Finally, we highlight the IUPHAR/MMV Guide to MALARIA PHARMACOLOGY, a web resource developed for the malaria research community that provides open and optimized access to published data on malaria pharmacology.
Topics: Humans; Malaria; Antimalarials; Drug Discovery; High-Throughput Screening Assays
PubMed: 37197802
DOI: 10.1111/bph.16144 -
Chembiochem : a European Journal of... Jun 2023Cladosporin, a unique natural product from the fungus Cladosporium cladosporioides, exhibits nanomolar inhibitory activity against Plasmodium falciparum by targeting its... (Review)
Review
Cladosporin, a unique natural product from the fungus Cladosporium cladosporioides, exhibits nanomolar inhibitory activity against Plasmodium falciparum by targeting its cytosolic lysyl-tRNA synthetase (PfKRS) to inhibit protein biosynthesis. Due to its exquisite selectivity towards pathogenic parasites, cladosporin has become a very promising lead compound for developing antiparasitic drugs to treat drug-resistant malaria and cryptosporidiosis infections. Here we review the recent research progress of cladosporin covering aspects of the chemical synthesis, biosynthesis, bioactivity, cellular target and structure-activity relationship.
Topics: Humans; Isocoumarins; Plasmodium falciparum; Malaria; Lysine-tRNA Ligase; Antimalarials; Malaria, Falciparum
PubMed: 37158666
DOI: 10.1002/cbic.202300154 -
Expert Opinion on Therapeutic Patents Mar 2023The efficacy of current therapeutic warheads in preventing malaria transmission or treating the disease is often hampered by the emergence of drug-resistance. No... (Review)
Review
INTRODUCTION
The efficacy of current therapeutic warheads in preventing malaria transmission or treating the disease is often hampered by the emergence of drug-resistance. No effective vaccines are available to date, and novel drugs able to counteract drug-resistant forms of malaria and/or to target multiple stages of the parasite's lifecycle are urgently needed.
AREAS COVERED
This review covers patents that protect antimalarial small molecules bearing the artemisinin or other chemical scaffolds, as well as vaccines, that have been published in the period 2015-2022. Literature was searched in public databases of articles and patents. Patents protecting small molecules that prevent malaria transmission are not discussed herein.
EXPERT OPINION
Significant progress has been made in the design of antimalarial agents. Most of these candidates have been tested in standardized strains, with the use of clinical isolates for testing still underdeveloped. Several compounds have been profiled in mouse models of malaria, including humanized mice. Despite having different efficacy, these new molecules might further progress the field and hopefully will advance to clinical development soon.
Topics: Humans; Animals; Mice; Antimalarials; Patents as Topic; Malaria; Plasmodium; Drug Resistance; Plasmodium falciparum
PubMed: 37060305
DOI: 10.1080/13543776.2023.2203814