Antimelanoma activity of 1,3,4-thiadiazolium mesoionics: a structure–activity relationship study

Senff‐Ribeiro, Andrea; Echevarrı́a, Aurea; Silva, Edson F.; Veiga, Sílvio Sanches; Oliveira, Maria Benigna Martinelli de

doi:10.1097/00001813-200403000-00012

Cited by 46 publications

(26 citation statements)

References 24 publications

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“…On the other hand, azoles are proven chemotherapeutic agents. Among the azoles, 1,3,4-thiadiazole and its derivatives are well known for its in vitro and in vivo anticancer activity (20,21). The 1,3,4-thiadiazoles induce early-phase apoptosis in human non-small lung cancer A549 cells through down-regulation of Bcl-XL and up-regulation of Bax expression (22).…”

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confidence: 99%

Synthesis, in vitro anticancer and antioxidant activity of thiadiazole substituted thiazolidin-4-ones

Joseph¹,

Shah²,

Kumar³

et al. 2013

Acta Pharmaceutica

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Reactive oxygen species (ROS) induced oxidative stress is believed to be a primary causative factor of various inflammatory diseases. ROS has been linked with cancer, coronary heart disease, and neurodegenerative diseases, and their presence in the body causes damage to the DNA of cells. Antioxidants exert their effects by scavenging or preventing the generation of ROS, which can protect the formation of free radicals and retard the progress of many chronic diseases, including cancer, inflammation, and car- A series of novel 5-alkyl/aryl thiadiazole substituted thiazolidin-4-ones were synthesized by a two-step process. In the first step, 5-alkyl/aryl substituted 2-aminothiadiazoles were synthesized, which on reaction with substituted aromatic aldehydes and thioglycolic acid in the presence of dicyclohexylcarbodiimide afforded thiazolidin-4-ones. All the compounds were synthesized in fairly good yields and their structures were confirmed by spectral and physical data. The title compounds were screened for in vitro anti-proliferative activity on human breast adenocarcinoma cells (MCF-7) by MTT assay. Most of the derivatives showed an IC 50 less than 150 µmol L -1 . Among the compounds tested, 2-(2-nitrophenyl)-3-(5-methyl-1,3,4-thiadiazol-2-yl)-thiazolidin-4-one (3f), 2-(3-fluorophenyl)-3-(5-methyl-1,3,4-thiadiazol-2--yl)-thiazolidin-4-one (3b), and 2-(4-chlorophenyl)-3--(5-methyl-1,3,4-thiadiazol-2-yl)-thiazolidin-4-one (3c) were found to be the most active derivatives with IC 50 values of 46.34, 66.84, and 60.71 µmol L -1 , respectively. Antioxidant studies of all the synthesized compounds were carried out by diphenylpicrylhydrazyl (DPPH) assay. Among the compounds tested, 2-phenyl-3-(5-styryl--1,3,4-thiadiazol-2-yl)-thiazolidin-4-one (3s) elicited superior antioxidant activity with IC 50 of 161.93 µmol L -1 .

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confidence: 99%

Synthesis, in vitro anticancer and antioxidant activity of thiadiazole substituted thiazolidin-4-ones

Joseph¹,

Shah²,

Kumar³

et al. 2013

Acta Pharmaceutica

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“…Many mesoionic derivatives possess useful biological activity [12,13,26,27]. The structural characteristics of mesoionic compounds, which contain distinct regions of positive and negative charges associated with a poly-heteroatomic system, enable them to cross cellular membranes and interact strongly with biomolecules.…”

Section: Resultsmentioning

confidence: 99%

Effect of mesoionic 4-phenyl-5-(cinnamoyl)-1,3,4-thiadiazolium-2-phenylamine chloride derivative salts on the activities of the nitric oxide synthase and arginase of Leishmania amazonensis

Soares‐Bezerra

Silva

Echevarrı́a

et al. 2008

Journal of Enzyme Inhibition and Medicinal Chemistry

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L-arginine is involved in the production of both nitric oxide (NO), mediated by nitric oxide synthase (NOS) and L-ornithine, by arginase activity. It is generally accepted that NO regulation occurs mainly at the transcriptional level of NOS. In a previous work we purported that there is evidence that Leishmania sp. can produce NO from L-arginine. An arginase activity in its gene sequence has also been reported in Leishmania parasites. In a search for intracellular targets as potential antileishmanicidal agents, such as the L-arginine metabolism, we used 1,3,4-thiadiazolium mesoionic compounds, that have been demonstrated to be cytotoxic to the Leishmania amazonensis, when compared to Pentamidine isethionate as a reference drug. Parasites were assayed in absence/presence of 4 0 -and 3 0 -methoxy mesoionic derivatives in order to verify the effect on NO production and arginase activity in L. amazonensis. The results indicated that the drugs reduce from 70 to 90% of the NO production by the parasite and act on a soluble nitric oxide synthase purified from L. amazonensis promastigotes and axenic amastigotes.

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“…25) The resonance signal of C 6 -H proton appears in the doublet form in the range about 7.8-7.5 ppm with the conjugation constant Jϭ8. 7 Hz, and C 3 -H in the range 6.5-6.4 with Jϭ2. 3 Hz.…”

Section: Chemistrymentioning

confidence: 98%

Evaluation of Antiproliferative Effect in Vitro of Some 2-Amino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole Derivatives

Matysiak¹

2006

CHEMICAL & PHARMACEUTICAL BULLETIN

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A great number of 1,3,4-thiadiazole derivatives display interesting antitumour activities iv vitro and in vivo conditions.1-10) Their mechanism of action is different for various types of substitution of 1,3,4-thiadiazole ring.11-15) Very promising for anticancer therapy seems to be the action connected with the apoptotic mechanisms and angiogenesis, which is a crucial step in the tumorgenesis. [16][17][18][19][20] Beside on this consideration we elaborated a new ringforming method for the synthesis of N-substituted 2-amino 5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles as a part of our antitumour and antifungal search program of compounds with resorcinol moiety.21) The presence of 2,4-dihydroxyphenyl substituent in the molecule is responsible first of all for its amphiphilic character. However, intensification of aminothiadiazole pharmacophore function and possibility of additional interactions via hydrogens bonds or van der Waal's forces with the potential molecular target can not be excluded. Moreover, relatively low level of toxicity of derivatives with 2,4-dihydroxyphenyl moiety is registered. 22,23) Recently, we have reported the synthesis and antiproliferative activity in vitro of some N-substituted 2-amino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole analogues. 24,25) It was found that N-alkyl and N-morpholinoalkyl derivatives exhibit significantly lower effect than phenyl ones. Some compounds showed stronger cytotoxic effect than cisplatin studied comparatively. The highest antiproliferative activity was found for the compounds with hydrophobic substituents (pϾ0) of electronwithdrawing character (sϾ0). 26)Extending the research in this area, we decided to obtain new derivatives, mainly differently substituted in N-aryl ring 2-phenylamino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles. Antiproliferative effect in vitro of compounds against panel of human cancer cell lines was established. Influence of Nsubstitution type on antitumour activity is discussed. ChemistryThe thiadiazole derivatives exemplified in this paper were prepared according to the route described in Fig. 1. 25) Treatment of sulfinylbis(2,4-dihydroxythiobenzoyl) (STB) with appropriate 4-substituted-3-thiosemicarbazides in methanol afforded N-substituted 2-amino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles (II-XIII). 2-Amino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole (I) was prepared from STB and semicarbazide hydrochloride. STB was obtained from 2,4-dihydroxybenzenecarbodithioic acid and SOCl 2 in diethyl ether. 25)In the 1 H-NMR spectrum of compound I the band in the 9.92 ppm corresponding to unsubstituted amine group is registered. The signal of proton of NH group substituted with the alkyl group is shift significantly in the range of higher fields (II). In the range of low fields as a rule there are registered two signals corresponding to protons of OH group in the resorcinol moiety.25) The resonance signal of C 6 -H proton appears in the doublet form in the range about 7.8-7.5 ppm with the conjugation constant Jϭ8.7 Hz, and C 3 -H in the range 6.5...

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Antimelanoma activity of 1,3,4-thiadiazolium mesoionics: a structure–activity relationship study

Cited by 46 publications

References 24 publications

Synthesis, in vitro anticancer and antioxidant activity of thiadiazole substituted thiazolidin-4-ones

Synthesis, in vitro anticancer and antioxidant activity of thiadiazole substituted thiazolidin-4-ones

Effect of mesoionic 4-phenyl-5-(cinnamoyl)-1,3,4-thiadiazolium-2-phenylamine chloride derivative salts on the activities of the nitric oxide synthase and arginase of Leishmania amazonensis

Evaluation of Antiproliferative Effect in Vitro of Some 2-Amino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole Derivatives

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