RESUMO
It is well known that cancer is the second leading cause of death worldwide. Due to this fact, new results for the treatment of cancer are constantly being introduced and verified. Imidazolidine derivatives regulate cell cycle progression and DNA stability. Structurally, a heterocyclic nucleus favors a direct DNA interaction and therefore, control of the DNA replication process. This review aims not only to discuss the role of imidazolidines in cancer therapy but also explore the functionality of such agents in the future aspects of cancer prognosis and treatment. Convincing data from 1996 to 2021 has presented imidazolidine derivatives as a relevant therapeutic tool to modulate cancer progression and malignancy. Here we highlight these aspects in a variety of cell lines, cancer types, involving in vitro and in vivo techniques.
Assuntos
Imidazolidinas , Neoplasias , DNA/metabolismo , Humanos , Imidazolidinas/metabolismo , Imidazolidinas/farmacologia , Imidazolidinas/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologiaRESUMO
Searching for new alternatives to antibiotic treatments is crucial to surmount the multidrug-resistant bacteria. In this work, the antimicrobial activity of synthetic imidazolidines was evaluated as well as their modulating effect on the resistance to fluoroquinolones in a S. aureus strain (SA-1199B), which overexpresses the norA gene that encodes the NorA efflux pump. Results showed weak antimicrobial activity (512 µg mL-1) for two fluorobenzylidene derivatives against this bacterial strain, while the other benzylidene derivatives were inactive. Despite this fact, both fluorinated compounds were able to enhance the activity of norfloxacin and ciprofloxacin against SA-1199B up to 6.4- and 3.2-fold, respectively. In addition, both derivatives potentiated the action of ethidium bromide against this strain, suggesting that the modulating effect probably involves the inhibition of the NorA efflux pump, which is in concordance with the fluorimetic assays and molecular docking analyses performed in this work.
Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Imidazolidinas/farmacologia , Proteínas Associadas à Resistência a Múltiplos Medicamentos/antagonistas & inibidores , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/química , Proteínas de Bactérias/metabolismo , Relação Dose-Resposta a Droga , Imidazolidinas/síntese química , Imidazolidinas/química , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Staphylococcus aureus/metabolismo , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
A new series of silver compounds could be of interest on designing new drugs for the treatment of leishmaniasis. The compounds [Ag(phen)(imzt)]NO3(1), [Ag(phen)(imzt)]CF3SO3(2), [Ag(phen)2](BF4)·H2O (3), [Ag2(imzt)6](NO3)2(4), and imzt have been synthesized and evaluated in vitro for antileishmanial activity against Leishmania. (L.) amazonensis (La) and L. (L.) chagasi (Lc), and two of them were selected for in vivo studies. In addition to investigating the action on Leishmania, their effects on the hydrogen peroxide production and cysteine protease inhibition have also been investigated. As for antileishmanial activity, compound (4) was the most potent against promastigote and amastigote forms of La (IC50 = 4.67 and 1.88 µM, respectively) and Lc (IC50 = 9.35 and 8.05 µM, respectively); and comparable to that of amphotericin B, reference drug. Beside showing excellent activity, it also showed a low toxicity. In the in vivo context, compound (4) reduced the number of amastigotes in the liver and spleen when compared to the untreated group. In evaluating the effect of the compounds on Leishmania, the level of hydrogen peroxide production was maintained between the lag and log phases; however, in the treatment with compound (4) it was possible to observe a reduction of 25.44 and 49.13%, respectively, in the hydrogen peroxide rates when compared to the lag and log phases. It was noticed that the presence of a nitrate ion and imzt in compound (4) was important for the modulation of the antileishmanial activity. Thus, this compound can represent a potentially new drug for the treatment of leishmaniasis.
Assuntos
Complexos de Coordenação/farmacologia , Imidazolidinas/farmacologia , Tionas/farmacologia , Tripanossomicidas/farmacologia , Animais , Complexos de Coordenação/síntese química , Complexos de Coordenação/toxicidade , Feminino , Imidazolidinas/síntese química , Imidazolidinas/toxicidade , Leishmania infantum/efeitos dos fármacos , Leishmania mexicana/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Mesocricetus , Camundongos , Testes de Sensibilidade Parasitária , Prata/química , Tionas/síntese química , Tionas/toxicidade , Tripanossomicidas/síntese química , Tripanossomicidas/toxicidadeRESUMO
BACKGROUND: Oxazolidinones derivatives exhibit different biological properties, including anticancer activity. This work aimed to investigate the anticancer potential of five novel 2-Thioxo-oxazolidin-4-one derivatives. METHODS: Cytotoxicity assays were performed in human peripheral blood mononuclear cells (PBMCs) from healthy individuals and seven tumor cell lines. Apoptosis detection and cell cycle were evaluated by flow cytometry and the expression of genes involved in cell death processes by Real-Time PCR. RESULTS: All oxazolinedione derivatives were not cytotoxic in PBMCs. NB-5 showed the best results in cancer cells, inhibiting the growth of all tumor cell lines tested. NB-4 exhibited the highest cytotoxicity in Jurkat cells (IC50=15.19µM) and NB-3 showed better anticancer effects in HL-60 (17.84µM). Only NB-4 significantly induced apoptosis in acute leukemia cells (p=0.001). All compounds caused a significant increase in expression of pro-apoptotic gene BID (p<0.05) and BECN1 (p<0.05). NB-3 significantly modulated the expression of RIPK3 (p=0.02) and DDIT3 (p=0.014), while NB-2 induced an increase of CDKN1A (p=0.03) and NB-4 induced PPARγ gene (p=0.0006). CONCLUSION: NB-5 showed antitumor effects in solid and hematopoietic cancer cells, while other derivatives produced higher activity against hematopoietic cells. In acute leukemia cells, oxazolidinone derivatives modulated the expression of genes involved in apoptosis, ER stress, necroptosis and inflammation.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Imidazolidinas/síntese química , Imidazolidinas/farmacologia , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Imidazolidinas/química , Leucócitos Mononucleares/efeitos dos fármacos , Estrutura MolecularRESUMO
INTRODUCTION:: Schistosomiasis is an infectious parasitic disease caused by trematodes of the genus Schistosoma, which threatens at least 258 million people worldwide and its control is dependent on a single drug, praziquantel. The aim of this study was to evaluate the anti-Schistosoma mansoni activity in vitro of novel imidazolidine derivatives. MATERIAL AND METHODS:: We synthesized two novel imidazolidine derivatives: (LPSF/PTS10) (Z)-1-(2-chloro-6-fluorobenzyl)-4-(4-dimethylaminobenzylidene)-5-thioxoimidazolidin-2-one and (LPSF/PTS23) (Z)-1-(2-chloro-6-fluoro-benzyl)-5-thioxo-4-(2,4,6-trimethoxy-benzylidene)-imidazolidin-2-one. The structures of two compounds were determined by spectroscopic methods. During the biological assays, parameters such as motility, oviposition, mortality and analysis by Scanning Electron Microscopy were performed. RESULTS:: LPSF/PTS10 and LPSF/PTS23 were considered to be active in the separation of coupled pairs, mortality and to decrease the motor activity. In addition, LPSF/PTS23 induced ultrastructural alterations in worms, after 24 h of contact, causing extensive erosion over the entire body of the worms. CONCLUSION:: The imidazolidine derivatives containing the trimetoxy and benzylidene halogens showed promising in vitro schistosomicidal activity.
Assuntos
Imidazolidinas/farmacologia , Células-Tronco de Sangue Periférico/efeitos dos fármacos , Schistosoma mansoni/efeitos dos fármacos , Esquistossomicidas/farmacologia , Animais , Humanos , Imidazolidinas/síntese química , Imidazolidinas/toxicidade , Camundongos , Microscopia Eletrônica de Varredura , Testes de Sensibilidade Parasitária , Schistosoma mansoni/ultraestrutura , Esquistossomicidas/síntese química , Esquistossomicidas/toxicidade , Fatores de TempoRESUMO
ABSTRACT Introduction: Schistosomiasis is an infectious parasitic disease caused by trematodes of the genus Schistosoma, which threatens at least 258 million people worldwide and its control is dependent on a single drug, praziquantel. The aim of this study was to evaluate the anti-Schistosoma mansoni activity in vitro of novel imidazolidine derivatives. Material and methods: We synthesized two novel imidazolidine derivatives: (LPSF/PTS10) (Z)-1-(2-chloro-6-fluorobenzyl)-4-(4-dimethylaminobenzylidene)-5-thioxoimidazolidin-2-one and (LPSF/PTS23) (Z)-1-(2-chloro-6-fluoro-benzyl)-5-thioxo-4-(2,4,6-trimethoxy-benzylidene)-imidazolidin-2-one. The structures of two compounds were determined by spectroscopic methods. During the biological assays, parameters such as motility, oviposition, mortality and analysis by Scanning Electron Microscopy were performed. Results: LPSF/PTS10 and LPSF/PTS23 were considered to be active in the separation of coupled pairs, mortality and to decrease the motor activity. In addition, LPSF/PTS23 induced ultrastructural alterations in worms, after 24 h of contact, causing extensive erosion over the entire body of the worms. Conclusion: The imidazolidine derivatives containing the trimetoxy and benzylidene halogens showed promising in vitro schistosomicidal activity.
Assuntos
Humanos , Animais , Camundongos , Imidazolidinas/farmacologia , Células-Tronco de Sangue Periférico/efeitos dos fármacos , Schistosoma mansoni/efeitos dos fármacos , Esquistossomicidas/farmacologia , Imidazolidinas/síntese química , Imidazolidinas/toxicidade , Microscopia Eletrônica de Varredura , Testes de Sensibilidade Parasitária , Schistosoma mansoni/ultraestrutura , Esquistossomicidas/síntese química , Esquistossomicidas/toxicidade , Fatores de TempoRESUMO
This paper describes the synthesis and in vitro biological activities of imidazolidine and hexahydropyrimidine derivatives against bacteria (Escherichia coli, Staphylococcus aureus and Mycobacterium tuberculosis) and Leishmania protozoa. Out of sixteen heterocyclic derivatives tested, none were cytotoxic against mammalian cells. The compounds showed significant bacterial effects and leishmanicidal activity. Compounds 4a and 4c were active against S. aureus and E. coli, respectively. Compounds 3a-3f, 4h and 4i presented promising results against M. tuberculosis, with MIC values ranging from 12.5 to 25.0 µg/mL, comparable to the "first and second line" drugs used to treat tuberculosis. Compounds 4a, 4c and 4e were active against L major. Three of them were structurally characterized by single-crystal X-ray diffraction.
Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Antiparasitários , Bactérias/efeitos dos fármacos , Imidazolidinas , Leishmania/efeitos dos fármacos , Pirimidinas , Animais , Antibacterianos/química , Antiparasitários/síntese química , Antiparasitários/química , Antiparasitários/farmacologia , Células Cultivadas , Cristalografia por Raios X , Humanos , Imidazolidinas/síntese química , Imidazolidinas/química , Imidazolidinas/farmacologia , Camundongos , Viabilidade Microbiana/efeitos dos fármacos , Modelos Moleculares , Estrutura Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Pirimidinas/síntese química , Pirimidinas/química , Pirimidinas/farmacologiaRESUMO
Imidazolidine derivatives are key components for the development of bioactive compounds for the treatment of many diseases, especially Chagas. In fact, others studies showed that the imidazolidine-2,4-dione has stood out by presenting a wide spectrum of pharmacological activities including anticonvulsants, antiarrhythmic, and antiparasitic. In the present study, we investigated the morphological alterations induced by imidazolidine derivates LPSF/NN-52 and LPSF/NN-100 on trypomastigotes forms of Trypanosoma cruzi through ultrastructural analysis by electron microscopy. Many concentrations were used to measure the antiparasitic propriety promoted by imidazolidine derivatives, and our study indicates that parasites treated with 13 µg mL(-1) of the imidazolidine derivates for 24 h revealed severe damage to the parasite's mitochondrial complex. Beyond that, also observed in treated parasites were the following: myelin bodies, enlargement of cytoplasm vacuole, fragmentation of endoplasmic reticulum, and some treated samples clearly showed signs of necrosis. To confirm the ultrastructural results, some assays were performed for knowledge cellular death induction promoted by imidazolidine derivates against immune spleen cells. The induction of the necrotic process through derivatives LPSF/NN-52 and LPSF/NN-100 showed similar results in relation to nifurtimox and benznidazole. In the last assays, it was demonstrated that NN-100 was efficient against epimastigotes and trypomastigotes forms and these results reinforce the mechanisms of action of both new imidazolidine derivatives against T. cruzi.
Assuntos
Imidazolidinas/química , Imidazolidinas/farmacologia , Tripanossomicidas/química , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Microscopia Eletrônica , Relação Estrutura-Atividade , Trypanosoma cruzi/ultraestruturaRESUMO
Schistosomiasis is a disease caused by helminthes of the genus Schistosoma, which threatens approximately 207 million people worldwide. Recently, strains of Schistosoma mansoni appear to be developing tolerance and resistance against Praziquantel, the most commonly available drug on the market used in the treatment of disease. This worrisome development justifies studies that seek alternatives for the prevention, treatment and cure of this disease. This study aimed to evaluate the in vitro activity of new imidazolidine compounds 1-benzyl-4-[(4-chloro-phenyl)-hydrazono]-5-thioxo-imidazolidin-2-one (LPSF/PT-5) and 1-(4-chloro-benzyl)-4-[(4-fluoro-phenyl)-hydrazono]-5-thioxo-imidazolidin-2-one (LPSF/PT-11) against adult worms of S. mansoni. LPSF/PT-5 and LPSF/PT-11 imidazolidine derivatives showed relevant schistosomicidal activity in vitro and induced significant ultrastructural alterations in worms and cell death: results similar to praziquantel. Thus, it is possible that these imidazolidine derivatives can be future candidates as schistosomotic drugs, but further studies are needed to elucidate the induced mechanisms behind this response.
Assuntos
Imidazolidinas/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose mansoni/parasitologia , Esquistossomicidas/farmacologia , Animais , Anexina A5/química , Apoptose/efeitos dos fármacos , Biomphalaria , Sobrevivência Celular/efeitos dos fármacos , Inibidores Enzimáticos/química , Feminino , Fluoresceína-5-Isotiocianato/química , Corantes Fluorescentes/química , Imidazolidinas/toxicidade , Indicadores e Reagentes/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Varredura , Necrose , Praziquantel/farmacologia , Praziquantel/toxicidade , Propídio/química , Schistosoma mansoni/ultraestrutura , Esquistossomose mansoni/tratamento farmacológico , Esquistossomicidas/toxicidade , Baço/citologia , Baço/efeitos dos fármacos , Baço/patologiaRESUMO
Schistosomiasis is a major public health problem with 207 million people infected and more than 779 million at risk. The drug of choice for treating schistosomiasis is praziquantel (PZQ); however, it is inefficient against immature forms of schistosomes. The aim of this study was to test new imidazolidine derivatives LPSF/PT09 and LPSF/PT10 against adult Schistosoma mansoni worms. IC50, cytotoxicity, immune response and cell viability assays were also available for these imidazolidines. Different concentrations of imidazolidine, from 32 to 320 »M, promoted motor abnormalities in breeding and unpaired worms, and death in 24 hours at higher concentrations. Although LPSF/PT09 and LPSF/PT10 did not affect IFN-³ and IL-10 production, they induced nitric oxide production and showed a similar behavior to praziquantel on cell death test. Thus, these new imidazolidine derivatives should undergo further study to develop schistosomiasis drugs.(AU)
Assuntos
Esquistossomose/patologia , Saúde Pública , Alergia e Imunologia/classificação , Imidazolidinas/farmacologiaRESUMO
This paper describes the preparation of N,N'-disubstituted ethylenediamine and imidazolidine derivatives and their in vitro biological activities against Leishmania species. Of the nine synthesized compounds, five displayed a good activity in both L. amazonensis and L. major promastigotes. The compounds 1,2-Bis(p-methoxybenzyl) ethylenediamine (4) and 1,3-Bis(p-methoxybenzyl)imidazolidines (5) showed the best activity on intracellular amastigotes, with IC50 values of 2.0 and 9.4 microgram/mL, respectively. In addition, none of compounds were cytotoxic against mammalian cells. The leishmanicidal activity can be related with inhibition of polyamine synthesis and cellular penetration within biological membranes.
Assuntos
Antiprotozoários/farmacologia , Etilenodiaminas/farmacologia , Imidazolidinas/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Animais , Antiprotozoários/síntese química , Antiprotozoários/química , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Etilenodiaminas/síntese química , Etilenodiaminas/química , Imidazolidinas/síntese química , Imidazolidinas/química , Leishmania/efeitos dos fármacos , Leishmania major/efeitos dos fármacos , Macrófagos Peritoneais/citologia , Macrófagos Peritoneais/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Modelos Químicos , Estrutura MolecularRESUMO
The only drug available for treating schistosomiasis is praziquantel, however there are already reports of resistance to its use in treatment, making it necessary to search and develop new compounds to combat schistosomiasis. We tested, in vitro, two new products, Laboratório de Planejamento de Síntese de Fármacos (LPSF)/5-(4-chloro-benzylidene-3-(4-nitrebenzyl)-4-thioxo-imidazolidin-2-one (RZS-2) and LPSF/5-(4-fluoride-benzylidene-3-(4-nitrebenzyl)-4-thioxo-imidazolidin-2-one (RZS-5) imidazolidines, against adult worms of Schistosoma mansoni. Efficacy and safety of these compounds were analyzed through IC50 cytotoxicity, immune response and cell viability tests. At different concentrations ranging from 40-640 microM, the imidazolidines produced motor abnormalities, inhibition of pairing and oviposition and mortality within 24 h at the higher concentrations. Although not triggering changes in IFN-gamma and IL-10, LPSF/RZS-2 and LPSF/RZS-5 induced production of nitric oxide and showed similar behavior to praziquantel in the cell death test.
Assuntos
Imidazolidinas/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Esquistossomicidas/farmacologia , Animais , Feminino , Imidazolidinas/administração & dosagem , Imidazolidinas/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Parasitária , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/parasitologia , Esquistossomicidas/administração & dosagem , Esquistossomicidas/imunologiaRESUMO
UNLABELLED: Finding new chemicals or adjuvants with analgesic effects in the central nervous system is clinically relevant due to the limited number of drugs with these properties. Here, we present PT-31, which is chemically related to 3-benzyl-imidazolidine, with an analgesic profile that results from alpha(2)-adrenoceptor activation. Intraperitoneal administration of PT-31 dose-dependently produced antinociception in the hot plate test, and interacted synergistically with morphine. This effect was completely reversed by yohimbine, a non-selective antagonist of alpha(2)-adrenoceptors, and by BRL 44408, a selective alpha(2A)-adrenoceptor antagonist. The combination of morphine and PT-31 produced greater antinociceptive activity than either alone, and isobolographic analysis revealed a synergistic interaction between these compounds. Docking results confirm the high affinity of the PT-31 ligand at the alpha(2A)-adrenoceptor. PERSPECTIVE: This study introduces a new analgesic compound (PT-31) that acts via alpha(2A)-adrenoceptor activation. A significant increase in analgesia was observed when co-administered with morphine. PT-31 is an interesting new substance for pain therapy.
Assuntos
Agonistas de Receptores Adrenérgicos alfa 2 , Agonistas alfa-Adrenérgicos/farmacologia , Analgésicos não Narcóticos/farmacologia , Analgésicos Opioides/farmacologia , Morfina/farmacologia , Antagonistas de Receptores Adrenérgicos alfa 2 , Agonistas alfa-Adrenérgicos/administração & dosagem , Agonistas alfa-Adrenérgicos/química , Antagonistas Adrenérgicos alfa/farmacologia , Analgésicos não Narcóticos/administração & dosagem , Analgésicos não Narcóticos/química , Animais , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Imidazóis/farmacologia , Imidazolidinas/administração & dosagem , Imidazolidinas/química , Imidazolidinas/farmacologia , Isoindóis/farmacologia , Masculino , Camundongos , Modelos Moleculares , Dor/tratamento farmacológico , Dor/metabolismo , Distribuição Aleatória , Receptores Adrenérgicos alfa 2/metabolismo , Ioimbina/farmacologiaRESUMO
Imidazolidine derivatives were studied as anti-Trypanosoma cruzi agents. Imidazolines can be considered as ethylenediamine/carbonyl precursors and therefore interfere with the biosynthesis of polyamines into the parasite. Some of the derivatives were found to have high and selective activity against the proliferative stages of the parasite, with IC(50) values against the epimastigote form in the low micromolar range as the reference drug Nifurtimox. The imidazolidines demonstrated to be stable after five days of incubation in buffer glucose, pH 7, indicating that diamines were not obtained in these conditions. But it was found that two of the studied diamine precursors were as active as the parent compounds. Probably, the imidazolidines affect the mitochondrial integrity according to the excreted end-products found in the NMR studies. The QSAR studies indicated that the bioactivities are correlated with the lipophilicities. In conclusion, we have described a new and relevant bioactivity for imidazolidines. The results support further in vivo studies of some of these imidazolidine derivatives.
Assuntos
Imidazolidinas/química , Imidazolidinas/farmacologia , Tripanossomicidas/química , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Etilenos/química , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
The emergence of strains of Schistosoma resistant to praziquantel has drawn attention to the search for new schistosomacide drugs. Imidazolidinic derivatives have performed outstandingly against adult S. mansoni worms when evaluated in vitro. The molecular modification of imidazolidine by way of bioisosteric replacement gives rise to variations in its biological response. This study verifies the potential of substituent groups in the derivatives (Z)3-benzyl-5-(2-fluoro-benzylidene)-imidazolidine-2,4-dione NE4, 3-benzyl-5-(4-chloro-arylazo)-4-thioxo-imidazolidin -2-ona PT5, 3-benzyl-5-(3-fluoro-benzylidene)-1-methyl-2-thioxo-imidazolidin-4-one JT53; 3-benzyl-1-methyl-5-(4-methyl-benzylidene)-2-thioxo-imidazolidin-4-one JT63; 3-benzyl-1-methyl-5-(4-methoxi-benzylidene)-2-thioxo -imidazolidin-4-one JT68; 3-(4-chloro-benzyl)-1-methyl-5-(4-methoxi-benzylidene)-2-thioxo-imidazolidin-4-one JT69; 3-(4-phenyl-benzyl)-1-methyl-5-(4-methoxi-benzylidene)-2-thioxo-imidazolidin-4-one JT72 by determining the viability in vitro of adult S. mansoni worms in the presence of these derivatives. The susceptibility of the worms obtained from mice and kept in culture in the presence of different concentrations was determined by way of schistosomacide kinetic, observed every 24 h over a period of eight days. The results show that the worms were more sensitive to the PT5 derivative at a concentration of 58 æM which killed 100 percent of the worms after 24 h of contact, also giving rise to alterations in the tegument surface of the worms with the formation of bubbles and peeling. These observations suggest a strong electronic contribution of the arylazo grouping in the biological response.
Assuntos
Animais , Feminino , Masculino , Camundongos , Imidazolidinas/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Esquistossomicidas/farmacologia , Imidazolidinas/síntese química , Testes de Sensibilidade Parasitária , Esquistossomicidas/síntese química , Fatores de TempoRESUMO
The emergence of strains of Schistosoma resistant to praziquantel has drawn attention to the search for new schistosomacide drugs. Imidazolidinic derivatives have performed outstandingly against adult S. mansoni worms when evaluated in vitro. The molecular modification of imidazolidine by way of bioisosteric replacement gives rise to variations in its biological response. This study verifies the potential of substituent groups in the derivatives (Z)3-benzyl-5-(2-fluoro-benzylidene)-imidazolidine-2,4-dione NE4, 3-benzyl-5-(4-chloro-arylazo)-4-thioxo-imidazolidin -2-ona PT5, 3-benzyl-5-(3-fluoro-benzylidene)-1-methyl-2-thioxo-imidazolidin-4-one JT53; 3-benzyl-1-methyl-5-(4-methyl-benzylidene)-2-thioxo-imidazolidin-4-one JT63; 3-benzyl-1-methyl-5-(4-methoxi-benzylidene)-2-thioxo -imidazolidin-4-one JT68; 3-(4-chloro-benzyl)-1-methyl-5-(4-methoxi-benzylidene)-2-thioxo-imidazolidin-4-one JT69; 3-(4-phenyl-benzyl)-1-methyl-5-(4-methoxi-benzylidene)-2-thioxo-imidazolidin-4-one JT72 by determining the viability in vitro of adult S. mansoni worms in the presence of these derivatives. The susceptibility of the worms obtained from mice and kept in culture in the presence of different concentrations was determined by way of schistosomacide kinetic, observed every 24 h over a period of eight days. The results show that the worms were more sensitive to the PT5 derivative at a concentration of 58 microM which killed 100% of the worms after 24 h of contact, also giving rise to alterations in the tegument surface of the worms with the formation of bubbles and peeling. These observations suggest a strong electronic contribution of the arylazo grouping in the biological response.
Assuntos
Imidazolidinas/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Esquistossomicidas/farmacologia , Animais , Feminino , Imidazolidinas/síntese química , Masculino , Camundongos , Testes de Sensibilidade Parasitária , Esquistossomicidas/síntese química , Fatores de TempoRESUMO
Synthesis and physico-chemical properties of 3-benzyl-5-(4-fluoro-benzylidene)-1-methyl-2-thioxo-imidazolidin-4-ones, 5-benzylidene-3-(4-nitro-benzyl)-2-thioxo-imidazolidin-4-ones and 4-acridin-9-ylmethylene-1-benzyl-5-thioxo-imidazolidin-2-ones compounds are described. These thioxo-imidazolidine derivatives were prepared by alkylation and condensation with 4-fluoro-benzaldehyde or nucleophilic Michael addition with cyanoacrylates. The schistosomicidal activity of 3-benzyl-5-(4-fluoro-benzylidene)-1-methyl-2-thioxo-imidazolidin-4-one compounds was evaluated.