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1.
Acta Trop ; 256: 107264, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38806090

ABSTRACT

Chagas disease (CD), caused by the flagellated protozoan Trypanosoma cruzi (T. cruzi), affects approximately 7 million people worldwide and is endemic in Latin America, especially among socioeconomically disadvantaged populations. Since the 1960s, only two drugs have been commercially available for treating this illness: nifurtimox (NFX) and benznidazole (BZN). Although these drugs are effective in the acute phase (AP) of the disease, in which parasitemia is usually high, their cure rates in the chronic phase (CP) are low and often associated with several side effects. The CP is characterized by a subpatent parasitaemia and absence of clinical symptoms in the great majority of infected individuals. However, at least 30 % of the individuals will develop potentially lethal symptomatic forms, including cardiac and digestive manifestations. For such reason, in the CP the treatment is usually symptomatic and typically focuses on managing complications such as arrhythmias, heart failure, or digestive problems. Therefore, the need for new drugs or therapeutic approaches using BZN or NFX is extremely urgent. This review presents the main clinical trials, especially in the CP, which involve BZN and NFX in different treatment regimens. Additionally, other therapies using combinations of these drugs with other substances such as allopurinol, itraconazole, ravuconazole, ketoconazole, posaconazole and amiodarone are also reported. The importance of early diagnosis, especially in pediatric patients, is also discussed, emphasizing the need to identify the disease in its early stages to improve the chances of successful treatment.


Subject(s)
Chagas Disease , Nifurtimox , Nitroimidazoles , Trypanocidal Agents , Trypanosoma cruzi , Chagas Disease/drug therapy , Humans , Nitroimidazoles/therapeutic use , Trypanosoma cruzi/drug effects , Trypanocidal Agents/therapeutic use , Nifurtimox/therapeutic use , Chronic Disease
2.
Molecules ; 19(12): 20374-81, 2014 Dec 05.
Article in English | MEDLINE | ID: mdl-25490429

ABSTRACT

A series of 14 (E)-cinnamic N-acylhydrazone derivatives, designed through molecular hybridization between the (E)-1-(benzo[d][1,3]dioxol-5-yl)-3-(4-bromophenyl)prop-2-en-1-one and (E)-3-hydroxy-N'-((2-hydroxynaphthalen-1-yl)methylene)-7-methoxy-2-naphthohydrazide, were tested for in vitro antiparasitic activity upon axenic amastigote forms of Leishmania donovani and bloodstream forms of Trypamosoma brucei rhodesiense. The derivative (2E)-3-(4-hydroxy-3-methoxy-5-nitrophenyl)-N'-[(1E)-phenylmethylene]acrylohydrazide showed moderate antileishmanial activity (IC50 = 6.27 µM) when compared to miltefosine, the reference drug (IC50 = 0.348 µM). However, the elected compound showed an excellent selectivity index; in one case it was not cytotoxic against mammalian L-6 cells. The most active antitrypanosomal compound, the derivative (E)-N'-(3,4-dihydroxybenzylidene)cinnamohydrazide (IC50 = 1.93 µM), was cytotoxic against mammalian L-6 cells.


Subject(s)
Antiprotozoal Agents/chemistry , Antiprotozoal Agents/pharmacology , Cinnamates/chemistry , Hydrazones/chemistry , Hydrazones/pharmacology , Leishmania donovani/drug effects , Molecular Structure , Parasitic Sensitivity Tests , Trypanosoma brucei rhodesiense/drug effects
3.
Molecules ; 18(3): 3445-57, 2013 Mar 15.
Article in English | MEDLINE | ID: mdl-23503118

ABSTRACT

Herein, we report the design, synthesis and trypanocidal activity of some novel trisubstituted imidazole derivatives. These heterocyclic derivatives were structurally planned by exploring the concept of molecular hybridisation between two arylhydrazones derived from megazol, which has potent trypanocidal activity. The trypanocidal activity of these triarylimidazole derivatives was evaluated against infective trypomastigote forms of T. cruzi and the derivative 2'-(4-bromophenyl)-1-methyl-5'-phenyl-1H,3'H-2,4'-biimidazol-3'-ol showed moderate biological activity (IC50 = 23.9 µM) when compared to benznidazole, a standard trypanocidal drug. These compounds did not present cytotoxic effects at concentrations near the trypanocidal IC50, being considered a good starting point for the development of new anti-Chagas drug candidates.


Subject(s)
Imidazoles/chemical synthesis , Trypanocidal Agents/chemical synthesis , Animals , Cell Line , Cell Survival/drug effects , Drug Evaluation, Preclinical , Hydrazones/chemistry , Imidazoles/pharmacology , Mice , Models, Molecular , Molecular Conformation , Trypanocidal Agents/pharmacology , Trypanosoma cruzi/drug effects
4.
Med Chem ; 7(6): 611-23, 2011 Nov.
Article in English | MEDLINE | ID: mdl-22313301

ABSTRACT

A series of 32 L-serinyl hydrazone derivatives have been synthesized and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv, being also evaluated their cell viabilities in non infected and infected macrophages with Mycobacterium bovis Bacillus Calmette-Guerin (BCG). The compounds 8c, 8e, 8h and 8i, were non-cytotoxic and exhibited an important minimum inhibitory concentration (MIC) activity between 25 and 100 µg/mL, which can be compared with that of the tuberculostatic drug D-cicloserine (5-20 µg/mL).


Subject(s)
Antitubercular Agents/pharmacology , Hydrazones/pharmacology , Mycobacterium tuberculosis/drug effects , Serine/pharmacology , Antitubercular Agents/chemical synthesis , Antitubercular Agents/chemistry , Cell Survival/drug effects , Cycloserine/chemistry , Cycloserine/pharmacology , Dose-Response Relationship, Drug , Hydrazones/chemical synthesis , Hydrazones/chemistry , Macrophages/drug effects , Macrophages/microbiology , Microbial Sensitivity Tests , Models, Molecular , Molecular Structure , Mycobacterium bovis/isolation & purification , Mycobacterium tuberculosis/cytology , Serine/chemical synthesis , Serine/chemistry , Stereoisomerism , Structure-Activity Relationship
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