Imidazole-Thiosemicarbazide Derivatives as Potent Anti-Mycobacterium tuberculosis Compounds with Antibiofilm Activity

Mycobacterium tuberculosis (Mtb) is an intracellular pathogenic bacterium and the causative agent of tuberculosis. This disease is one of the most ancient and deadliest bacterial infections, as it poses major health, social and economic challenges at a global level, primarily in low- and middle-income countries. The lack of an effective vaccine, the long and expensive drug therapy, and the rapid spread of drug-resistant strains of Mtb have led to the re-emergence of tuberculosis as a global pandemic. Here, we assessed the in vitro activity of new imidazole-thiosemicarbazide derivatives (ITDs) against Mtb infection and their effects on mycobacterial biofilm formation. Cytotoxicity studies of the new compounds in cell lines and human monocyte-derived macrophages (MDMs) were performed. The anti-Mtb activity of ITDs was evaluated by determining minimal inhibitory concentrations of resazurin, time-kill curves, bacterial intracellular growth and the effect on biofilm formation. Mutation frequency and whole-genome sequencing of mutants that were resistant to ITDs were performed. The antimycobacterial potential of ITDs with the ability to penetrate Mtb-infected human macrophages and significantly inhibit the intracellular growth of tubercle bacilli and suppress Mtb biofilm formation was observed.

Erythrocytic antioxidant system in the administration of new coordination compounds thiosemicarbazide derivatives

Background: Currently, there is a growing interest in new local coordination compounds (CC), which demonstrated antitumor properties, but their influence on the erythrocyte antioxidant system has not been studied. The aim of the study: to study the effects of CC, thiosemicarbazide derivatives –TIA-160, CMT-67 and CMJ-33 on indices of the antioxidant system indicators in erythrocytes peripheral blood in vivo experiments. Material and methods: The action of CC on superoxide dismutase, catalase, total antioxidant capacity was evaluated on a group of 34 white rats, randomly divided into 4 groups: the first control group was injected subcutaneously with saline. The other groups (2 – TIA-160, 3 – CMT-67 and 4 – CMJ-33) were given subcutaneously 3 times a week for 30 days, 0.1µM / kg CC. Results: It was established that the TIA-160 compound demonstrated the highest capacity to induce the expression of erythrocyte catalase that exceeded the control level of 1.8, which did not correlate with the enzymatic superoxide dismutase (SOD) activity. Thus, this study showed that there are differences in the mechanisms of action of thiosemicarbazone derivatives. Conclusions: The influence of tested CC on the indices of the antioxidant system is selective. This selectivity may be the base to their strong selective antiproliferative and cytotoxic action on tumor cells, but not on healthy ones.

Optimized Synthesis of New Thiosemicarbazide Derivatives with Tuberculostatic Activity

Original results are presented in the field of research that addresses the extension of the reaction of residue of acyl-thiosemicarbazide fixation on the structure of 5-nitrobenzimidazole by a sulphonic group. The aim of the study is the increase of new thiosemicarbazide derivatives’ applicative potential in the field of biochemistry, with a wide range of medical applications. The newly obtained compounds were characterized by using elemental analysis and spectral analysis (FT-IR and 1H NMR). A study regarding the optimization of the chemical reactions was made. The performed in vitro biological tests confirmed the tuberculostatic activity of three newly obtained compounds against Mycobacterium tuberculosis.

Design, Synthesis, Antimicrobial Evaluation and Molecular Docking Studies of Some Novel Monoterpenoids Substituted Quinoxaline Thiosemicarbazide Derivatives

Owing to the increasingly serious problems caused by multidrug resistance in acquired infection pathogens, it has become an urgent need to develop new classes of antibiotics for overcoming the resistance. The present study aims to increase the antimicrobial activity of quinoxaline thiosemicarbazide derivatives by introducing a hydrophobic alkyl chain, an electron-releasing group in the ring, and substitution by some acyclic, cyclic and bicyclic monoterpenes and their antimicrobial evaluation against various strains with molecular docking studies. The lead molecule (1E, 4E)-1-(7-chloro-3-isopropyl- quinoxalin-2(1H)-ylidene) thiosemicarbazide was synthesized and condensed with various monoterpenes to synthesize different derivatives. The structures of compounds were confirmed through IR., NMR & mass spectroscopy. The synthesized derivatives were evaluated in vitro for antibacterial and antifungal activities against various strains using the agar dilution method. Molecular docking studies of the derivatives (Va– Vg) were performed to find out essential binding sites against target protein (PDB: 3 FAP, receptor: FKBP 12) using Autodock 4.2. The compounds Va, Vd, Vf & Vg exhibited potent antibacterial and antifungal activity. Among all these compounds Vd was found to exhibit more potent activity against gram +Ve, gram –Ve bacterial and fungal strains at MIC 0.19 μg/ml, 0.39μg/ml, and 1.56 μg/ml respectively. The docking studies of all the compounds exhibit potent binding energy, but the compound Vd exhibit interactive binding energy (-9.98 kcal/mol) to the active pockets of the receptor FKBP12. The compound Vd interacting with various active sites of amino acids of receptors like PHE128, TRP190, TYR26, VAL55, ILE56, PHE99, and TRP59. In terms of structure- activity relationship study it is revealed that the activity profile against bacterial and fungal strains was altered by the formation of monoterpenoid substituted (1E, 4E)-1-(7- chloro-3-isopropylquinoxalin-2(1H)-ylidene) thiosemicar- bazide derivatives. The study reveals that bicyclic monoterpenes substituted compounds exhibit greater activity than cyclic and acyclic. The molecular docking studies also showed that all the compounds exhibit good docking energy to bind and inhibit the FKBP12 receptor.

An Updated Review on Synthesis and Biological Activities of Thiosemicarbazide Analogs

This review paper focuses on the different synthetic methodologies that researchers have adopted to synthesize various thiosemicarbazide derivatives with different biological activities of synthesized compounds in the last 20 years. Most of the investigations available in the literature are directed to the biological activities of thiosemicarbazide derivatives with less discussion on its synthetic schemes. This review article presents various reaction scheme, which has been adopted for thiosemicarbazide derivative synthesis along with the reported pharmacological activities of synthesized analogs. The available literature in the article aims to encourage more studies on the synthesis of thiosemicarbazide derivatives, which will help for drug discovery having thiosemicarbazide nucleus.

Synthesis, Characterization and antioxidant activities of Semicarbazide and Thiosemicarbazide Derivatives

In this research work Semicarbazide, thiosemicarbazide derivatives 3 to 25 were synthesized by conventional methods with high percentage yield and reaction rate. 1H-NMR and EIMS spectroscopic techniques were used to elucidate the structure of the synthesized compounds. The effect of thiosemicarbazide and semicarbazide derivatives as an antioxidant agents were studied by DPPH free radical scavenging, ferric ion reducing, ferrous ion chelating assays. Higher DDPH radical scavenging activity exhibited by most of the compounds as compared to standard vitamin C. Excellent ferric ion reducing activity was indicated by compounds of theseriesas compared to standard vitamin C. However most of the compounds generally showed average ferrous ion chelating activity than standard EDTA.