scholarly journals Antimalarial Inhibitors Targeting Epigenetics or Mitochondria in Plasmodium falciparum: Recent Survey upon Synthesis and Biological Evaluation of Potential Drugs against Malaria

Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5711
Author(s):  
Christina L. Koumpoura ◽  
Anne Robert ◽  
Constantinos M. Athanassopoulos ◽  
Michel Baltas
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Infectious Diseases ◽  
Dna Methyltransferases ◽  
Biological Evaluation ◽  
Dihydroorotate Dehydrogenase ◽  
Drug Candidates ◽  
The Past ◽  
Synthesis And Biological Evaluation ◽  
Epigenetic Processes

Despite many efforts, malaria remains among the most problematic infectious diseases worldwide, mainly due to the development of drug resistance by P. falciparum. Over the past decade, new essential pathways have been emerged to fight against malaria. Among them, epigenetic processes and mitochondrial metabolism appear to be important targets. This review will focus on recent evolutions concerning worldwide efforts to conceive, synthesize and evaluate new drug candidates interfering selectively and efficiently with these two targets and pathways. The focus will be on compounds/scaffolds that possess biological/pharmacophoric properties on DNA methyltransferases and HDAC’s for epigenetics, and on cytochrome bc1 and dihydroorotate dehydrogenase for mitochondrion.

scholarly journals Synthesis and Antiplasmodial Activity of Novel Fosmidomycin Derivatives and Conjugates with Artemisinin and Aminochloroquinoline

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4858 ◽  
Author(s):  
Despina Palla ◽  
Antonia I. Antoniou ◽  
Michel Baltas ◽  
Christophe Menendez ◽  
Philippe Grellier ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Infectious Diseases ◽  
Antimalarial Activity ◽  
Biological Evaluation ◽  
Antiplasmodial Activity ◽  
Malaria Parasites ◽  
Antimalarial Agents ◽  
New Compounds

Malaria, despite many efforts, remains among the most problematic infectious diseases worldwide, mainly due to the development of drug resistance by Plasmodium falciparum. The antibiotic fosmidomycin (FSM) is also known for its antimalarial activity by targeting the non-mevalonate isoprenoid synthesis pathway, which is essential for the malaria parasites but is absent in mammalians. In this study, we synthesized and evaluated against the chloroquine-resistant P. falciparum FcB1/Colombia strain, a series of FSM analogs, derivatives, and conjugates with other antimalarial agents, such as artemisinin (ART) and aminochloroquinoline (ACQ). The biological evaluation revealed four new compounds with higher antimalarial activity than FSM: two FSM-ACQ derivatives and two FSM-ART conjugates, with 3.5–5.4 and 41.5–23.1 times more potent activities than FSM, respectively.

Synthesis and Biological Evaluation of C-Aromataxane Derivatives as P-Glycoprotein-Mediated Multi Drug Resistance Reversal Agents

Heterocycles ◽  
2015 ◽  
Vol 90 (1) ◽  
pp. 482
Author(s):  
Takayuki Doi ◽  
Naoko Yamaguchi ◽  
Kosuke Ohsawa ◽  
Kazuoki Nakai ◽  
Masahito Yoshida ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Biological Evaluation ◽  
Multi Drug Resistance ◽  
Reversal Agents ◽  
P Glycoprotein ◽  
Resistance Reversal ◽  
Synthesis And Biological Evaluation

scholarly journals Design, synthesis and biological evaluation of novel fungicides for the management of Fusarium DieBack disease

2019 ◽  
Vol 62 (3) ◽  
Author(s):  
Israel Bonilla Landa ◽  
Osvaldo León De la Cruz ◽  
Diana Sánchez Rangel ◽  
Randy Ortiz Castro ◽  
Benjamin Rodriguez Haas ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antifungal Activity ◽  
Fusarium Solani ◽  
Antifungal Agents ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Dieback Disease ◽  
Synthetic Chemist ◽  
Fusarium Dieback ◽  
Synthesis And Biological Evaluation

Abstract. Fusarium Dieback, a new and lethal insect-vectored disease can host over 300 tree species including the avocado trees. This problem has recently attracted the attention of synthetic chemist not only to develop new triazol antifungal agents but also due to severe drug resistance to “classic” triazol antifungal agents. Here, a series of novel antifungal triazoles with a p-trifluoromethylphenyl moiety were synthesized and characterized by spectroscopic and spectrometric methods. Most of the target compounds synthesized showed from modest to good inhibitory activity and less phytotoxicity in comparison with the commercially available propiconazol; in particular, compounds 7 and 13 were active against both Fusarium solani and Fusarium euwallaceae. The results showed that compounds 7, 13, and 4 have great potential to be developed as new antifungal agents because of both good antifungal activity and low phytotoxicity. SAR showed that free alcohols and not O-protected compounds significantly influence the activity. Hence, a-methyl-a-1,2,4-triazole emerged as novel compound to develop new ketone-triazole-type antifungal agents for the management of Fusarium Dieback disease Resumen. Fusarium Dieback es una nueva enfermedad letal transmitida por insectos que actúan como vectores y puede atacar a más de 300 especies de árboles, incluidos los árboles de aguacate. Recientemente, este problema ha atraído la atención de los químicos sintéticos para desarrollar nuevos agentes antifúngicos triazólicos debido a la resistencia severa que desarrollan los insectos a los agentes antifúngicos triazólicos "clásicos". Durante este trabajo, se sintetizaron nuevos triazoles antifúngicos que contienen un grupo p-trifluorometilfenilo y se caracterizaron por métodos espectroscópicos y espectrométricos. La mayoría de los compuestos diana sintetizados mostraron una actividad inhibidora de modesta a buena y menos fitotoxicidad en comparación con el propiconazol que es comercialmente disponible; en particular, los compuestos 7 y 13 mostraron ser activos contra Fusarium solani y Fusarium euwallaceae. Los resultados mostraron que los compuestos 7, 13 y 4 tienen un gran potencial para desarrollarse como nuevos agentes antifúngicos debido a la buena actividad antifúngica y su baja fitotoxicidad. SAR mostró que los alcoholes libres y no los compuestos O-protegidos influyen significativamente en la actividad. Por lo tanto, el α-metil-α-1,2,4-triazol surgió como un nuevo compuesto líder para desarrollar nuevos agentes antifúngicos tipo cetona-triazol para el tratamiento de la enfermedad Fusarium Dieback.

scholarly journals Synthesis and Biological Evaluation of Febrifugine Analogues

2014 ◽  
Vol 9 (12) ◽  
pp. 1934578X1400901
Author(s):  
Huong Doan Thi Mai ◽  
Giang Vo Thanh ◽  
Van Hieu Tran ◽  
Van Nam Vu ◽  
Van Loi Vu ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antimalarial Activity ◽  
Biological Evaluation ◽  
Strong Inhibition ◽  
Synthetic Analogues ◽  
Synthetic Compounds ◽  
Activity Evaluation ◽  
Synthesis And Biological Evaluation

A series of febrifugine analogues were designed and synthesized. Antimalarial activity evaluation of the synthetic compounds indicated that these derivatives had a strong inhibition against both chloroquine-sensitive and -resistant Plasmodium falciparum parasites. Many of them were found to be more active than febrifugine hydrochloride. The tested analogues had also a significant cytotoxicity against four cancer cell lines (KB, MCF7, LU1 and HepG2). Among the synthetic analogues, two compounds 17b and 17h displayed a moderate cytotoxicity while they exhibited a remarkable antimalarial activity.

scholarly journals Total synthesis and biological evaluation of fluorinated cryptophycins

2012 ◽  
Vol 8 ◽  
pp. 2060-2066 ◽  
Author(s):  
Christine Weiß ◽  
Tobias Bogner ◽  
Benedikt Sammet ◽  
Norbert Sewald
Keyword(s):  
Total Synthesis ◽  
Tumor Cell ◽  
Biological Evaluation ◽  
Significant Loss ◽  
Drug Resistant ◽  
Tumor Cell Lines ◽  
Cytotoxicity Assays ◽  
The Past ◽  
Highly Active ◽  
Synthesis And Biological Evaluation

Cryptophycins are cytotoxic natural products that exhibit considerable activities even against multi-drug-resistant tumor cell lines. As fluorinated pharmaceuticals have become more and more important during the past decades, fluorine-functionalized cryptophycins were synthesized and evaluated in cell-based cytotoxicity assays. The unit A trifluoromethyl-modified cryptophycin proved to be highly active against KB-3-1 cells and exhibited an IC50 value in the low picomolar range. However, the replacement of the 3-chloro-4-methoxyphenyl-substituent in unit B by a pentafluorophenyl moiety resulted in a significant loss of activity.

scholarly journals An Overview on the Therapeutics of Neglected Infectious Diseases—Leishmaniasis and Chagas Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Brindha J ◽  
Balamurali M. M ◽  
Kaushik Chanda
Keyword(s):  
Infectious Diseases ◽  
Chagas Disease ◽  
Biosynthetic Pathway ◽  
Neglected Tropical Diseases ◽  
Nucleoside Analogs ◽  
Severe Toxicity ◽  
Drug Candidates ◽  
Chemical Structures ◽  
The Past ◽  
Associated Proteins

Neglected tropical diseases (NTDs) as termed by WHO include twenty different infectious diseases that are caused by bacteria, viruses, and parasites. Among these NTDs, Chagas disease and leishmaniasis are reported to cause high mortality in humans and are further associated with the limitations of existing drugs like severe toxicity and drug resistance. The above hitches have rendered researchers to focus on developing alternatives and novel therapeutics for the treatment of these diseases. In the past decade, several target-based drugs have emerged, which focus on specific biochemical pathways of the causative parasites. For leishmaniasis, the targets such as nucleoside analogs, inhibitors targeting nucleoside phosphate kinases of the parasite’s purine salvage pathway, 20S proteasome of Leishmania, mitochondria, and the associated proteins are reviewed along with the chemical structures of potential drug candidates. Similarly, in case of therapeutics for Chagas disease, several target-based drug candidates targeting sterol biosynthetic pathway (C14-ademethylase), L-cysteine protease, heme peroxidation, mitochondria, farnesyl pyrophosphate, etc., which are vital and unique to the causative parasite are discussed. Moreover, the use of nano-based formulations towards the therapeutics of the above diseases is also discussed.

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