37536-32-6

Upstream product

• 69-72-7 salicylic acid 
• 119-36-8 methyl salicylate 
• 5351-69-9 4-Phenyl-3-thiosemicarbazide 
• 1441-87-8 salicyloyl chloride 
• 103-72-0 phenyl isothiocyanate 
• 936-02-7 2-Hydroxybenzoylhydrazine 

Downstream Products

• 81518-26-5 5-(2-hydroxyphenyl)-4-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-thione 
• 94507-86-5 2-(5-(phenylamino)-1,3,4-oxadiazol-yl)phenol 
• 94565-97-6 5-(2-hydroxyphenyl)-2-phenylamino-2,4-dihydro-3H-1,3,4-thiadiazole 
• 81518-26-5 4-phenyl-5-(2'-hydroxyphenyl)-3-mercapto-1,2,4-triazole 
• 135815-44-0 Pd(C₆H₅NHCSNHNHCOC₆H₄-o-OH)Cl₂ 
• 122448-07-1 bis-[5-(2-hydroxy-phenyl)-4-phenyl-4H-[1,2,4]triazol-3-yl]-disulfide 
• 81518-37-8 2-(5-Butylsulfanyl-4-phenyl-4H-[1,2,4]triazol-3-yl)-phenol 
• 81518-36-7 2-(4-Phenyl-5-propylsulfanyl-4H-[1,2,4]triazol-3-yl)-phenol 
• 81518-34-5 2-(5-Ethylsulfanyl-4-phenyl-4H-[1,2,4]triazol-3-yl)-phenol 
• 81518-35-6 2-(5-Allylsulfanyl-4-phenyl-4H-[1,2,4]triazol-3-yl)-phenol 

Relevant academic research and scientific papers

Pharmacomodulations of the benzoyl-thiosemicarbazide scaffold reveal antimicrobial agents targeting D-alanyl-D-alanine ligase in bacterio

D-Alanyl-D-alanine ligase (Ddl) is a validated and attractive target among the bacterial enzymes involved in peptidoglycan biosynthesis. In the present work, we investigated the pharmacomodulations of the benzoylthiosemicarbazide scaffold to identify new Ddl inhibitors with antibacterial potency. Five novel series of thiosemicarbazide analogues, 1,2,4-thiotriazole-3-thiones, 1,3,4-thiadiazoles, phenylthiosemicarbazones, diacylthiosemicarbazides and thioureas were synthesized via straightforward procedures, then tested against Ddl and on susceptible or resistant bacterial strains. Among these, the thiosemicarbazone and thiotriazole were identified as the most promising scaffolds with Ddl inhibition potency in the micromolar range. Antimicrobial evaluation of salicylaldehyde-4(N)-(3,4-dichlorophenyl) thiosemicarbazone 33, one of the best compounds in our study, revealed interesting antimicrobial activities with values of 3.12–6.25 μM (1.06–2.12 μg/mL) against VRE strains and 12.5–25.0 μM (4.25–8.50 μg/mL) towards MRSA and VRSA strains. A detailed mechanistic study was conducted on the Ddl inhibitors 4-(3,4-dichlorophenyl)-5-(2-hydroxyphenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione 20 and compound 33, and revealed a bactericidal effect at 5 × MIC concentration after 7 h and 24 h, respectively, and a bacteriostatic effect at 1 × MIC or 2 × MIC without any sign of bacterial membrane disruption at these lower concentrations. Finally, 20 and 33 were proved to target Ddl in bacterio via intracellular LC-MS dosage of D-Ala, L-Ala and D-Ala-D-Ala. Although, at this stage, our results indicate that other mechanisms might be involved to explain the antimicrobial potency of our compounds, their ability to inhibit the growth of strains resistant to usual antibiotics, as well as strains that express alternative ligases, sets the stage for the development of new antimicrobial agents potentially less sensitive to resistance mechanisms.

1-(2-Hydroxybenzoyl)-thiosemicarbazides are promising antimicrobial agents targeting D-alanine-D-alanine ligase in bacterio

The bacterial cell wall and the enzymes involved in peptidoglycan synthesis are privileged targets for the development of novel antibacterial agents. In this work, a series of 1-(2-hydroxybenzoyl)-thiosemicarbazides inhibitors of D-Ala-D-Ala ligase (Ddl) were designed and synthesized in order to target resistant strains of bacteria. Among these, the 4-(3,4-dichlorophenyl)-1-(2-hydroxybenzoyl)-3-thiosemicarbazide 29 was identified as a potent Ddl inhibitor with activity in the micromolar range. This compound, possessing strong antimicrobial activity including against multidrug resistant strains, was proven to act through a bactericidal mechanism and demonstrated very low cytotoxicity on THP-1 human monocytic cell line. Inhibition of Ddl activity by 29 was confirmed in bacterio using UPLC-MS/MS by demonstrating an increase in D-Ala intracellular pools accompanied by a commensurate decrease in D-Ala-D-Ala. Further structure-activity relationships (SARs) studies provided evidence that the hydroxyl substituent in the 2-position (R1) of the benzoylthiosemicarbazide scaffold is essential for the enzymatic inhibition. This work thus highlights the 1-(2-hydroxybenzoyl)-thiosemicarbazide motif as a very promising tool for the development of novel antibacterial compounds acting through an interesting mechanism of action and low cytotoxicity.

Design, Synthesis and Antibacterial Evaluation of 1-[(1R,2S)-2-Fluorocyclopropyl]ciprofloxacin-1,2,4-triazole-5(4H)-thione Hybrids

A new class of 1-[(1R,2S)-2-fluorocyclopropyl]ciprofloxacin (CPFX)-1,2,4-triazole-5(4H)-thione hybrids 6a?–?6o was designed, synthesized and evaluated for their in?vitro antibacterial activities against a panel of clinically important drug-sensitive and d

Synthesis and biological evaluation of 1, 2, 4-triazoles and 1, 3, 4-oxadiazoles derivatives linked to 1, 4-dihydropyridines scaffold

A series of diethyl-2, 6-dimethyl-4-phenyl-1, 4-dihydropyridine-3, 5-dicarboxylate derivative coupled to 1, 3, 4-oxadiazole-5-thiones and 1, 2, 4-triazole-5-thiones moieties at C2, C6 positions of 1, 4-dihydropyridine ring system was prepared. This linkage was carried out by the reaction of 1, 3, 4-oxadiazole-5-thiones and 1, 2, 4-triazole-5-thiones with 2, 6-dibromomethyl-3, 5-diethoxycarbonyl-4-phenyl-1, 4-dihydropyridine in the presence of potassium carbonate as a weak base and dry acetone as the solvent. The newly synthesized compounds were characterized by FT-IR, 1H NMR, 13C NMR spectral data, elemental analysis and FAB-MS. The synthesized compounds were tested for their antimicrobial and antifungal activity against Escherichia coli and Aspergillus fumigatus in vitro in comparison with Enrofloxacin and Amphotericin as the reference drugs which are normally used for treating such infections. The synthetic compounds showed different inhibition zones against tested bacteria and fungi. Compound 8d showed more antagonistic activity against E. coli and A. fumigatus.

Synthesis of a series of novel tetra-tert-butylcalix[4]arene linked to 1,2,4-triazole and 1,3,4-oxadiazole derivatives

A series of tetra-tert-butylcalix[4]arene linked to 1,2,4-triazole-5-thiones and 1,3,4-oxadiazole-5-thiones derivatives at lower rim were synthesized by the reaction of 1,2,4-triazole-5-thione and 1,3,4-oxadiazole-5-thione with 5,11,17,23-tetra-tert-butyl-25,27-bis(3-bromopropoxy)-26,28-dihydroxycalix[4]arene (2). The synthesized compounds were characterized by FT-IR, 1H NMR, 13C NMR spectral data, elemental analysis and ESI-MS.

Structure-activity relationship studies of microbiologically active thiosemicarbazides derived from hydroxybenzoic acid hydrazides

Forty-five derivatives of thiosemicarbazide were synthesized, and their antibacterial activity against Gram-positive and Gram-negative bacteria was evaluated. Some of the described compounds exhibited interesting activity against reference strains of Gram

Synthesis of some 1,3,4-thiadiazole derivatives as inhibitors of Entamoeba histolytica

In the quest for potent anti-amoebic agents, some 1,3,4-thiadiazole derivatives were synthesized and characterized by spectral data. The purity of the compounds was confirmed by elemental analysis. All the compounds were screened in vitro against HM1:IMSS strain of Entamoeba histolytica by microdilution method. The results revealed that compounds 1 (IC50 = 0.670 μM), 3 (IC50 = 1.60 μM) and 8 (IC50 = 0.522 μM) had much better anti-amoebic activity than the reference drug metronidazole (IC50 = 1.80 μM). Further, cytotoxicity of the compounds having IC50 value less than metronidazole was assessed by MTT assay on human breast cancer MCF-7 cell line and all the compounds were found low cytotoxic in the concentration range of 2.5-250 μM. Preliminary results indicate that these three compounds (1, 3 and 8) may be subjected to further investigations and it may be hoped that the present study will stimulate efforts towards the development of novel effective anti-amoebic agents.

Influence of pH values on the self-assembly in three trinuclear nickel complexes with bridging ligand N-salicylyl 4-phenyl-thiosemicarbazide

Three trinuclear nickel complexes containing N-salicylyl 4-phenyl-thiosemicarbazide(abbreviated as spt3-) have been synthesized. They are complex [Ni3(spt)2(dpt)2]·2C3H7NO (1) with 2,5-diphenylamiyl 1,3,4 thiodiazone ligand(dpt) and the other two complexes without dpt ligand ([Ni3(spt)2(H2O)4]·2C3H7NO (2) and [Ni3(spt)2(C5H5N)2(H2O)2]·2C3H7NO (3)). Central Ni atom and two terminal Ni atoms in the three complexes are combined by two bridging deprotonated spt3- ligands, forming a strictly linear trinuclear nickel structure unit with a Ni{single bond}N{single bond}N{single bond}Ni{single bond}N{single bond}N{single bond}Ni core. There is an extended 1D structure in 2 and 3 formed by intermolecular hydrogen bonds O{single bond}H...O. The influence of pH of the reaction medium upon the composition of the final products is discussed.

Synthesis of 5-aryl-3-glycosylthio-4-phenyl-4H-1,2,4-triazoles and their acyclic analogs under conventional and microwave conditions

Under microwave irradiation (MWI), 4-phenyl-5-substituted-4H-1,2,4- triazole-3-thiol derivatives 7 and 8 were synthesized in a good yield by intramolecular cyclization of the aroyl phenyl thiosemicarbazides 5 and 6. The respective triazolylglycosides (Str-glycosides) 12-17 were obtained by reaction of triazoles 7 and 8 with glycosyl halides 9-11 in dry acetone in the presence of potassium carbonate as base under both conventional and MWI conditions. Alkylation of 7 and 8 with haloalchols 18-20 in boiling ethanolic solution containing sodium ethoxide as a base gave the corresponding alkylated analogs 21-26. MWI conditions led to higher yield in shorter reaction time than the conventional method. Treatment of 26 with tosyl chloride gave the unexpected product 29 and not 27 or 28. Oxidation of 26 with sodium metaperiodate afforded triazole 8 and not the aldehyde 30. Attempted glycosylation and alkylation of the phenolic OH group in triazole 8 were unsuccessful; this was proved by theoretical calculations using the AM1 semi-empirical method. (Chemical Equation Presented). Copyright Taylor & Francis Group, LLC.