Synthesis and Antimicrobial Activity of Novel Thiazole Substituted Pyrazole Derivatives

Gaikwad, Nitin D.; Patil, Sachin; Bobade, Vivek D.

doi:10.1002/jhet.1513

Cited by 31 publications

(29 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, there is a real need for new therapeutic options for the treatment of cryptococcosis. With this goal, and based on the wide range of biological activities exhibited by thiazole heterocycles [16,17,18], we report here the synthesis and screening of thiazole heterocyclic compounds (Figure 1 and 2) with therapeutic potential against cryptococcosis. Some of these molecules have shown promising antifungal activity in vitro.…”

Section: A N U S C R I P Tmentioning

confidence: 99%

Thiazole compounds with activity against Cryptococcus gattii and Cryptococcus neoformans in vitro

Sá

Lino

Fonseca

et al. 2015

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

Section: A N U S C R I P Tmentioning

confidence: 99%

Thiazole compounds with activity against Cryptococcus gattii and Cryptococcus neoformans in vitro

Sá

Lino

Fonseca

et al. 2015

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

“…Thiosemicarbazones and their thiazole heterocyclic derivatives are of great importance in pharmacology due to their broad range of biological activities, such as anticonvulsant, antimicrobial, and antiparasitic activities (Gaikwad, Patil, Bobade, 2013;Souza et al, 2013;Bharti et al, 2010;Siddiqui et al, 2009;Oliveira et al, 2008a;Souza, 2005;Dimmock et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and cytotoxicity evaluation of thiosemicarbazones and their thiazole derivatives

Braga

Fonseca

Ramos

et al. 2016

Braz. J. Pharm. Sci.

View full text Add to dashboard Cite

The aims of this study were to synthesize a series of thiosemicarbazones and their thiazole derivatives, to investigate their cytotoxic activity against three human cancers and normal (Vero cells) cell lines, and to evaluate the pro-apoptotic potential of the most active compounds. Materials and Methods: The thiosemicarbazones were obtained by reacting an aromatic aldehyde with thiosemicarbazide (yield 71-96%), which were subjected to a cyclization with α-bromoacetophenone to yield the required thiazole heterocycles (yield 63-100%). All the synthesized compounds were screened at 50 µM concentration against three cell lines representing HL60 (promyelocytic leukemia), Jurkat (acute lymphoblastic leukemia), and MCF-7 (breast cancer). The pro-apoptotic effect was measured by flow cytometry as the percentage of cells with hypodiploid DNA. Results: Three thiazole compounds showed activity against at least one tumor cell line (IC 50 = 43-76 µM) and low cytotoxicity against Vero cells (IC 50 > 100 µM). The most active compound of this series induced 91% and 51% DNA fragmentation in HL60 and MCF-7 cell lines, respectively, suggesting that this compound triggered apoptosis in these cells. Conclusion: Among the synthesized compounds, one in particular was found to exert antiproliferative and pro-apoptotic activity on tumor cells and can be considered promising as a lead molecule for the design of new analogues with improved activity.Uniterms: Thiosemicarbazones/synthesis. Thiosemicarbazones/cytotoxic activity. Thiazoles/derivatives/ synthesis. Thiazoles/derivatives/cytotoxic activity. O estudo teve como objetivo a síntese de uma série de tiossemicarbazonas e seus derivados tiazólicos e a avaliação da atividade citotóxica contra três linhagens de células tumorais humanas e células normais (Vero), a fim de se avaliar o potencial pró-apoptótico dos compostos mais ativos. As tiossemicarbazonas foram obtidas por reação entre um aldeído aromático e tiossemicarbazida (rend. 71-96%), as quais foram submetidas à ciclização com α-bromoacetofenona, fornecendo os heterociclos tiazólicos desejados (rend. 63-100%). Todos os compostos sintetizados foram testados na concentração de 50 µM contra três linhagens de células tumorais: HL60 (leucemia promielocítica), Jurkat (leucemia linfoblástica aguda) e MCF-7 (câncer de mama). O efeito pró-apoptótico foi avaliado por citometria de fluxo como porcentagem de células com DNA hipodiplóide. Três compostos tiazólicos foram ativos contra, pelo menos, uma linhagem tumoral (CI 50 =43-76 µM), com baixa citotoxicidade contra células Vero (CI 50 > 100 µM). O composto mais ativo dessa série induziu fragmentação do DNA de 91% e 51% nas linhagens HL60 e MCF-7, respectivamente, sugerindo que este composto ativou a apoptose nessas células. Dentre os compostos sintetizados, um em particular apresentou atividade antiproliferativa e pró-apoptótica em células tumorais e pode ser considerado composto protótipo promissor na busca por novos análogos com atividade melhorada.

show abstract

“…The thiazole compounds, which possess sulfur and nitrogen, are widely distributed in natural products and have promising biological activity, representing a class of substances that attracts great synthetic interest (21). Some studies have reported the synthesis of new thiazoles with anti-inflammatory, antibacterial, anticancer, and anti-HIV activities (22)(23)(24)(25).…”

mentioning

confidence: 99%

Heterocycle Thiazole Compounds Exhibit Antifungal Activity through Increase in the Production of Reactive Oxygen Species in the Cryptococcus neoformans-Cryptococcus gattii Species Complex

Sá

Lima

Lino

et al. 2017

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Human cryptococcosis can occur as a primary or opportunistic infection and develops as an acute, subacute, or chronic systemic infection involving different organs of the host. Given the limited therapeutic options and the occasional resistance to fluconazole, there is a need to develop novel drugs for the treatment of cryptococcosis. In this report, we describe promising thiazole compounds 1, 2, 3, and 4 and explore their possible modes of action against Cryptococcus. To this end, we show evidence of interference in the Cryptococcus antioxidant system. The tested compounds exhibited MICs ranging from 0.25 to 2 g/ml against Cryptococcus neoformans strains H99 and KN99␣. Interestingly, the knockout strains for Cu oxidase and sarcosine oxidase were resistant to thiazoles. MIC values of thiazole compounds 1, 2, and 4 against these mutants were higher than for the parental strain. After the treatment of C. neoformans ATCC 24067 (or C. deneoformans) and C. gattii strain L27/01 (or C. deuterogattii) with thiazoles, we verified an increase in intracellular reactive oxygen species (ROS). Also, we verified the synergistic interactions among thiazoles and menadione, which generates superoxides, with fractional inhibitory concentrations (FICs) equal to 0.1874, 0.3024, 0.25, and 0.25 for the thiazole compounds 1, 2, 3, and 4, respectively. In addition, thiazoles exhibited antagonistic interactions with parasulphonatephenyl porphyrinato ferrate III (FeTPPS). Thus, in this work, we showed that the action of these thiazoles is related to an interference with the antioxidant system. These findings suggest that oxidative stress may be primarily related to the accumulation of superoxide radicals.

show abstract

Synthesis and Antimicrobial Activity of Novel Thiazole Substituted Pyrazole Derivatives

Cited by 31 publications

References 36 publications

Thiazole compounds with activity against Cryptococcus gattii and Cryptococcus neoformans in vitro

Thiazole compounds with activity against Cryptococcus gattii and Cryptococcus neoformans in vitro

Synthesis and cytotoxicity evaluation of thiosemicarbazones and their thiazole derivatives

Heterocycle Thiazole Compounds Exhibit Antifungal Activity through Increase in the Production of Reactive Oxygen Species in the Cryptococcus neoformans-Cryptococcus gattii Species Complex

Contact Info

Product

Resources

About