Thiosemicarbazide Derivatives Research Articles

Synthesis of modified 1,3,4-thiadiazole incorporating substituted thiosemicarbazide derivatives: Elucidating the in vitro and in silico studies to develop promising anti-diabetic agent

Hybrid molecules based on the 1,3,4-thiadiazole were always the choice of different researchers due to their significant application in medicinal as well as pharmaceutical application. In the present study, twenty analogs of 1,3,4-thiadiazole-bearingthiosemicarbazide moiety (1–20) were synthesized and screened for their anti-diabetic profile. The synthesized compounds were spectroscopically characterized through different spectroscopic techniques such as 1HNMR, 13CNMR, and HREI-MS. Comparing the whole set of afforded compounds to the standard glimepiride drugs (16.01 ± 0.02 μM), the inhibition profiles against α-amylase ranged from 21.02 ± 0.08 to 54.08 ± 0.04 μM. Comparing synthetic analogs to normal glimepiride (IC50 = 14.06 ± 0.05 μM), the range of α-glucosidase activity was likewise variable, ranging from 18.04 ± 0.07 μM to IC50 = 51.05 ± 0.03 μM (against α-glucosidase). Compound 19 demonstrated high potency among the produced analogs since it had both ortho-nitrosubstitution at the aryl ring. The pattern of substitutions around the aryl ring was used for all analogs to determine the structure–activity relationship. In addition, a molecular docking study was conducted on the potent analogs to examine the interactions between the active residues of the targeted enzymes with the synthesized compound. The synthesized molecule showed different types of interactions with amino acid. The outcome demonstrates that these compounds provide several essential interactions with the active sites of enzymes, hence strengthening their enzymatic activity for the future prediction as drug competitors.

Synthesis of novel carbazole hydrazine-carbothioamide scaffold as potent antioxidant, anticancer and antimicrobial agents

BackgroundCarbazole-based molecules containing thiosemicarbazide functional groups are recognized for their diverse biological activities, particularly in enhancing therapeutic anticancer effects through inhibiting crucial pathways. These derivatives also exhibit noteworthy antioxidant properties.ObjectivesThis study aims to synthesize, characterize, and evaluate the antioxidant and anticancer activities of 18 novel carbazole derivatives.MethodsThe radical scavenging capabilities of the compounds were assessed using the 2,2-diphenyl-1-picrylhydrazyl assay. Antiproliferative activities were evaluated on MCF-7 cancer cell lines through viability assays. Additionally, the modulation of the PI3K/Akt/mTOR pathway, apoptosis/necrosis induction, and cell cycle analysis were conducted for the most promising anticancer agents.Resultsnine compounds showed potent antioxidant activities with IC50 values lower than the positive control acarbose, with compounds 4 h and 4y exhibiting the highest potency (IC50 values of 0.73 and 0.38 µM, respectively). Furthermore, compounds 4o and 4r displayed significant anticancer effects, with IC50 values of 2.02 and 4.99 µM, respectively. Compound 4o, in particular, exhibited promising activity by targeting the PI3K/Akt/mTOR signaling pathway, inhibiting tumor survival, inducing apoptosis, and causing cell cycle arrest in MCF-7 cell lines. Furthermore, compound 4o was showed significant antimicrobial activities against S. aureus and E. coli, and antifungal effect against C. albicans. Its potential to overcome drug resistance through this pathway inhibition highlights its promise as an anticancer agent. Molecular docking simulations supported these findings, revealing favorable binding profiles and interactions within the active sites of the enzymes PI3K, AKT1, and mTOR. Moreover, assessing the druggability of the newly synthesized thiosemicarbazide derivatives demonstrated optimal physicochemical properties, further endorsing their potential as drug candidates.

New Antibacterial 1,3,4-Thiadiazole Derivatives With Pyridine Moiety.

1,3,4-Thiadiazole compounds were synthesized using pyridine carboxylic acid derivatives and thiosemicarbazide derivatives. The molecular structures of the resulting compounds were characterized by spectroscopic methods such as ATR-FTIR, 1H-NMR, and elemental analysis. Its compounds were also examined for their antibacterial properties against some strains of bacteria. Five synthesized compounds showed varying antibacterial effects on Escherichia coli, Salmonella kentucky, Bacillus substilis and Klebsiella pneumoniae. This result revealed that some of the resulting compounds could be antibacterial agents.

Design and synthesis of novel 1,3,4-thiadiazole thioglycosides as promising antimicrobial potent structures

Thiosemicarbazide was used as a key starting material for the building of a diversity of novel heterocyclic moieties. The heterocyclization reaction of thiosemicarbazide derivatives with carbon disulfide in basic conditions afforded novel heterocyclic 1,3,4-thiadiazolethiolate derivatives. 1,3,4-thiadiazole-2-thiol was successfully reacted with protected α-D-gluco- and galacto-pyranosyl bromides in dimethylformamide at room temperature to give the matching 1,3,4-thiadiazole S-glycosides in good yields. The latter compounds were reacted with ammonia-methanol at room temperature for 10 min, and the deprotected derivatives were obtained in good yields. The newly synthesized compounds were characterized by basic analyses and spectral information (IR,1H NMR, and 13C NMR, X-ray). All newly produced compounds were evaluated and screened for their antibacterial activities. Compound 6f proved to be the most active antimicrobial among the investigated heterocycles.

New Thiosemicarbazide Derivatives with Multidirectional Biological Action.

Over the years, several new medicinal substances have been introduced for the treatment of diseases caused by bacteria and parasites. Unfortunately, due to the production of numerous defense mechanisms by microorganisms and parasites, they still pose a serious threat to humanity around the world. Therefore, laboratories all over the world are still working on finding new, effective methods of pharmacotherapy. This research work aimed to synthesize new compounds derived from 3-trifluoromethylbenzoic acid hydrazide and to determine their biological activity. The first stage of the research was to obtain seven new compounds, including six linear compounds and one derivative of 1,2,4-triazole. The PASS software was used to estimate the potential probabilities of biological activity of the newly obtained derivatives. Next, studies were carried out to determine the nematocidal potential of the compounds with the use of nematodes of the genus Rhabditis sp. and antibacterial activity using the ACCT standard strains. To determine the lack of cytotoxicity, tests were performed on two cell lines. Additionally, an antioxidant activity test was performed due to the importance of scavenging free radicals in infections with pathogenic microorganisms. The conducted research proved the anthelmintic and antibacterial potential of the newly obtained compounds. The most effective were two compounds with a 3-chlorophenyl substituent, both linear and cyclic derivatives. They demonstrated higher efficacy than the drugs used in treatment.

The Importance of Substituent Position for Antibacterial Activity in the Group of Thiosemicarbazide Derivatives.

The search for new antibacterial compounds is still a huge challenge for scientists. Each new chemotherapy drug is not 100% effective when introduced into treatment. Bacteria quickly become resistant to known structures. One promising group of new compounds is thiosemicarbazides. In the presented work, we looked for the relationship between structure and antibacterial activity within the group of thiosemicarbazide derivatives. This is a continuation of our previous work. Here, we decided to check to what extent the position of the 3-methoxyphenyl substituent affects potency. We obtained new structures that differ in the positions of the substituent in the thiosemicarbazide skeleton. Based on the obtained results of the biological tests, it can be concluded that the substituent in position 1 of thiosemicarbazide derivatives significantly determines their activity. Generally, among the substituents used, trifluoromethylphenyl turned out to be the most promising. The MIC values for compounds with this substituent are 64 µg/mL towards Staphylococci sp. Using molecular docking, we tried to explain the mechanism behind the antibacterial activity of the tested compounds.

Structure-activity relationship and cytotoxicity of the new thiosemicarbazide derivatives and their Cu(II) complexes against prostate and melanoma cancer cells

In this study, eighteen new ligands (B1–B18) containing a thiosemicarbazide core were synthesized and characterized in terms of physicochemical properties, molecular docking and in vitro biological activity. The structures of eleven ligands were investigated using X-Ray diffraction and Hirschfeld Surface analysis. To study the structure-activity relationship, the organic ligands contained pyridin-2-ylmethyl, pyridin-3-ylmethyl or pyridin-4-ylmethyl moieties and various substituents. Their pharmakokinetic profiles and molecular docking results suggest high potential as new drug candidates. The complexing ability of the selected organic ligands was also evaluated, yielding five new Cu(II) complexes (Cu(B1)Cl2, Cu(B4)Cl2, Cu(B10)Cl2, Cu(B17)Cl2, Cu(B18)Cl2). The obtained results suggest the formation of the polymeric structures. All organic ligands and Cu(II) complexes were tested for anticancer activity against prostate and melanoma cancer cells (PC-3, DU-145, LNCaP, A375, G-361, SK-MEL-28) and normal fibroblasts (BJ), as well as antimicrobial activity against six selected bateria strains. Among B1–B18 compounds, B3, B5, B9, B10, B12 and B14 exhibited cytotoxic activity. The studied Cu(II) complexes were in general more active, with Cu(B1)Cl2 exhibiting antincancer activity agains all three prostate cancer cells and Cu(B10)Cl2 reaching the IC50 value equal to 88 μM against G-361 melanoma cells. Several compounds also exhibited antimicrobial activity against gram-positive and gram-negative bacteria. It was found that the type of specific substituents, especially the presence of -chloro and -dichloro substituents had a greated impact on the cytotoxicity than the position of the nitrogen atom in the pyridylacetyl moiety.

Green approach to synthesize novel thiosemicarbazide complexes, characterization; DNA-methyl green assay and in-silico studies against DNA polymerase

A thiosemicarbazide derivative as (E)-4-ethyl-1-(1-(naphthalen-1-yl) ethylidene) thiosemicarbazide (HAN) was synthesized then characterized to prepare [Co(HAN)Cl2·(H2O)2], [Ni(HAN)Cl2·(H2O)2]. H2O, and [Cd(HAN)Cl2] complexes. According to spectral and analytical data we could confirm the neutral bidentate mode of bonding via (C]S) and (C]N) groups to form 1:1 M ratio within the three complexes. The octahedral geometry was suggested for Co(II) and Ni(II) complexes according to electronic transitions assigned to 4T1g → 4T1g(P)(ʋ2) and 4T1g → 4A2g(F)(ʋ3) and 3A2g → 3T1g(P,υ3) and 3A2g → 3T1g(F,υ2), respectively. The values of nephelauetic ratio (β) in the ligand field parameters detect the ionic nature of new M-L bonds. The molecular ion peaks appeared in the mass spectra of two selected complexes confirming their molecular formulae. The conductometric study was performed for Cd(II) ion solution during variable additions of HAN to calculate association and formation constant of Cd(II)-HAN complex. DFT/B3LYP method was used to optimize the structures of the compounds and confirm the binding mode of the ligand. The distribution of C(5) = N(17) and C(13) = S(19) groups asserts their priority in coordination. Hirshfeld crystal properties were obtained via normalized contact distance (dnorm) and shape index in which the nitrogen atoms act as the best contact points in crystal packing. The biological screening was carried out against microbial strains as well as methyl green/DNA test. In vitro, the superiority of the ligand was clearly recorded in its biological effectiveness. In silico methods were implemented to confirm the activity of the ligand and to recognize the interaction features. The bioavailability, pharmacokinetics and drug-likeness were evaluated via Swiss-link. The data detect the ability of the ligand to penetrate barrier of brain (BBB) but not absorbed in gastrointestinal tract. Pharmit link and molecular docking were utilized to investigate the interaction of HAN with 1bna, 425d and 2k4l proteins. The best intercalation with protein pockets was observed with 2k4l protein, and searching the MolPort library detects a drug analog of MolPort-002-894-701. Finally, the results suggest the biological efficiency of the ligand, which may be asserted by specialists through intensive in-vivo studies.

Multifaceted bioactivity of thiosemicarbazide derivatives: Synthesis, characterization, and DFT investigations on inhibition of α-amylase, hydroxyl radical scavenging, and iron chelating activities with molecular docking insights

In this study, eight bioactive thiosemicarbazide derivatives (3a-h) were synthesized and characterized through 1HNMR , 13CNMR and Mass spectroscopic techniques. Finally, their inhibition activities against α-amylase and antioxidant activity were investigated. Among the synthetic series, five compounds 3 g (IC50 = 8.61 ± 1.42 µM) 3a (IC50 = 13.41 ± 1.65 µM), 3e (IC50 = 15.23 ± 1.17 µM), 3 h (IC50 = 17.37 ± 0.87 µM) and 3d (IC50 = 17.95 ± 1.99 µM) showed excellent inhibition by comparing with standard (acarbose, IC50 = 21.55 ± 1.31 µM). Similarly, in the case of iron chelating agent activity, product compounds 3a-h presented outstanding activity in the range of IC50 = 18.19 ± 1.81 to 63.42 ± 1.45 µM superior than standard (EDTA, IC50 = 66.43 ± 1.07 µM) while in hydroxyl radical scavenging activity all the synthesized products 3a-h also showed excellent scavenging activity in the range of IC50 values 25.85 ± 1.13 to 58.9 ± 2.95 µM when compared to standard vitamin C (IC50 = 60.51 ± 1.02 µM). We expanded our investigation to molecular interactions via a docking study, where these compounds were docked with the target protein to unveil their binding affinities and key interactions, offering additional insights into their inhibitory mechanisms. The chemical nature of the synthesized compounds was revealed through density functional theory (DFT) calculations at B3LYP/6–311++G(d,p). Intramolecular hydrogen bonding was explored using DFT-d3 and reduced density gradient (RDG) analysis. Additionally, various reactivity parameters were investigated through TD-DFT at the CAM-B3LYP/6–311++G(d,p) method.

تخليق(توليف) مشتقات الثيوسيمياكاربازيد الالدهيدية في وسط كحولي

Thiosemicarbazide derivatives (3a-c) were synthesized by reacting Thiosemicarbazide with aromatic aldehydes in an alcoholic medium. The reaction was monitored by TLC, and the structural composition of the derivatives was confirmed by melting point, IR, and ¹HNMR spectroscopy. Thiosemicarbazide derivatives are important in the biological field and can form complexes with some transition elements. Keywords:Thiosemicarbazide , Aldehehydes, Synthesis, Derivatives.

Design, synthesis and molecular modeling studies of thiosemicarbazide & thiazolyl-hydrazone derivatives as potential anticancer agents and topoisomerase inhibitors

This study involved the design, synthesis and evaluation of a series of novel thiosemicarbazide and thiazolyl-hydrazone derivatives. The synthesized compounds were tested for cytotoxic effects SH-SY5Y neuroblastoma cells, as well as NIH-3T3 normal cell line using the MTT assay. Among the tested compounds, 3b, 3d, 3i, 4b, 4d and 4i exhibited IC50 values ranging from 1.97 µM to 3.22 µM in the SH-SY5Y cancer cell line with lower cytotoxicity toward NIH-3T3 cells. Moreover, all compounds were also screened for their topoisomerase I and II inhibitory activity and compound 3b completely inhibited the topoisomerase I enzyme, whereas all compounds showed potent topoisomerase II inhibitory activity. Docking studies were performed to identify the mode of binding of the tested compounds to the active site of topoisomerase I and II. In conclusion, N-(4-(2-((2-chlorophenyl)carbamothioyl)hydrazine-1-carbonyl)phenyl)benzamide (3b) emerges as a promising inhibitor of topoisomerase I and II and holds potential as a lead compound in the quest for novel anticancer agents.

Some pyrimidohexahydroquinoline candidates: synthesis, DFT, cytotoxic activity evaluation, molecular docking, and in silico studies.

Some hexahydroquinoline candidates were prepared by reacting 2-amino-3-cyano-1-cyclohexylhexahydroquinoline with oxalyl chloride and triethyl orthoformate. The computational chemical approach agreed with the product-testing results. The produced substances were examined in vitro for their antiproliferative activity against liver carcinoma (HepG2), breast adenocarcinoma (MCF7), prostate cancer (PC3), and colon cancer (HCT116) cell lines. The highest potency against the four cell lines was exhibited by hydrazide, thiosemicarbazide, and thiazolidinone derivatives. The best docking score was presented by thiosemicarbazide and thiazolidinone derivatives as they showed the highest binding to the Mcl-1 enzyme with binding energies of -8.97 and -8.90 kcal mol-1, respectively, which were higher than that of the co-crystallized ligand (LC3) with a binding energy of -8.74 kcal mol-1. Besides, the modeling pharmacokinetics disclosed their desirable drug-likeness and oral bioavailability characteristics.

On the pivotal role of tetrel bonding in the supramolecular architectures of PbII–NCS complexes with chelating thiosemicarbazide derivatives

Detailed analysis of 1D and 2D supramolecular polymeric aggregations in Pb-complexes, driven by Pb⋯NCS and Pb⋯SCN tetrel bonds.

Synthesis and in Vitro Antimicrobial Evaluation of Novel Potent Bioactive Heterocyclic Compounds

In the present work, the antibacterial and antifungal properties of six new heterocyclic Schiff bases (HSb1, HSb2, HSb3, HSb4, HSb5, HSb6) were evaluated as potential bioactive compounds against the disease-causing pathogenic microorganisms (S.epidermidis, S.aureus, B.cereus RSKK863, E.aerogenes, P.aeroginosa sp., K. pneumonia, S. type H, P.vulgaris, E. coli and (C.albicans Y-1200-NIH). The well-diffusion-method was used to determine the antimicrobial activity. For this purpose, heterocyclic Schiff bases were synthesized by condensation reaction of aldehyde derivatives and thiosemicarbazide derivatives. Spectral analysis techniques (organic elemental analysis, FT-IR,1H-NMR, HRMS, SEM-EDX) were used to characterize the synthesized compounds. It was determined that all the newly synthesized heterocyclic Schiff bases exhibited sound, high or moderate inhibitory effects on the growth of selected different standard antibiotics.

Exploring the synthesis, structure, spectroscopy and biological activities of novel 4-benzylidene-1-(2-(2,4-dichloro phenyl)acetyl) thiosemicarbazide derivatives: An integrated experimental and theoretical investigation

BackgroundNovel α-amylase inhibitors play a crucial role in managing diabetes and obesity, contributing to improved public health by addressing these challenging and prevalent conditions. Moreover, the synthesis of anti-oxidant agents is essential due to their potential in combating oxidative stress-related diseases and promoting overall health. ObjectiveSynthesis of thoisemicarbazone derivatives of 2,4-dichlorophenyl acetic acid and to screened them for their biological activities. MethodThiosemicarbazone derivatives (4–13) were synthesized by refluxing 2,4-dichlorophenyl acetic acid with sulfuric acid in ethanol to get the ester (2), which was further refluxed with thiosemicarbazide to get compound (3). Finally, different aromatic aldehydes were refluxed with compound (3) in ethanol in catalytic amount of acetic acid to obtained the final products (4–13). Using modern spectroscopic techniques including HR-ESI-MS, 13C-, and 1H NMR, the structures of the created derivatives were confirmed. ResultsThe synthesized derivatives showed excellent to good inhibitory activity in the range of IC50 values of 4.95 ± 0.44 to 69.71 ± 0.05 µM against α-amylase enzyme when compared to standard drug acarbose (IC50 = 21.55 ± 1.31 µM). In case of iron chelating activity, these products showed potent activity better than standard EDTA (IC50 = 66.43 ± 1.07 µM) in the range of IC50 values of 22.43 ± 2.09 to 61.21 ± 2.83 µM. However, the obtained products also show excellent to good activity in the range of IC50 values of 28.30 ± 1.17 to 64.66 ± 2.43 µM against hydroxyl radical scavenging activity when compared with standard vitamin C (IC50 = 60.51 ± 1.02 µM). DFT used to calculate different reactivity factors including ionization potential, electronegativity, electron affinity, chemical softness, and chemical hardness were calculated using frontier molecular orbital (FMO) computations. The molecular docking studies for the synthesized derivatives with α-amylase were carried out using the AutoDock Vina to understand the binding affinities with active sites of the protein.

Electrochemical synthesis of some thiosemicarbazide derivatives doped polypyrrole electrodes and supercapacitor applications

Thiosemicarbazide derivatives (TSC, N-Phenyl TSC, N-Cyclohexyl TSC) doped polypyrrole (PPy) based electrodes were synthesized in one step electropolymerization method. It was determined that thiosemicarbazide derivatives had an effect on the morphological and chemical structure of PPy. Among the thiosemicarbazide derivatives, it was determined that the additive of PPy that had the highest and most curative effect on the electrochemical energy storage performance was determined to be N-Cyclohexyl TSC, and its effects on the electrochemical performance at different concentrations were investigated. The PPy/N-Cyclohexyl TSC (2.5 mM) electrode exhibited a capacitance of 300.5 F/g at a potential operating range of 1.1 V, in 0.5 M H2SO4 electrolyte, and the current density of 0.5 A/g. The symmetrical supercapacitor device obtained using PPy/N-Cyclohexyl TSC (2.5 mM) electrode showed capacitance retention rate of 90.4% and 81.5% in 0.5 M H2SO4 and 1.0 M Na2SO4 electrolytes and at the end of the 5000 cycles life cycle test, respectively. In addition, the PPy/N-Cyclohexyl TSC (2.5 mM)/ PPy/N-Cyclohexyl TSC (2.5 mM) symmetrical supercapacitor device exhibits a specific capacitance of 175 F/g at a current density of 0.4 A/g in 0.5 M H2SO4, while 137.3 F/g in 1.0 M Na2SO4 electrolyte. The energy and power density values obtained at 0.5 M H2SO4 and 1.0 M Na2SO4 for the supercapacitor device were 8.7 Wh/kg, 343.4 W/kg and 19.1 Wh/kg, 883.5 W/kg, respectively.

Novel Quinoline-Based Thiosemicarbazide Derivatives: Synthesis, DFT Calculations, and Investigation of Antitubercular, Antibacterial, and Antifungal Activities.

The discovery of new antimicrobial agents as a means of treating drug-resistant microbial pathogens is of utmost significance to overcome their immense risk to human well-being. The current investigation involves the development, synthesis, and assessment of the antimicrobial efficacy of novel quinoline derivatives incorporating a thiosemicarbazide functionality. To design the target compounds (QST1-QST14), we applied the molecular hybridization approach to link various thiosemicarbazides to the quinoline core with a sulfonyl group. Upon the synthesis and completion of structural characterization via spectroscopic techniques (1H NMR, 13C NMR, 15N NMR, IR, and HRMS), the title molecules were extensively evaluated for their potential antitubercular, antibacterial, and antifungal activities. N-(3-Chlorophenyl)-2-(quinolin-8-ylsulfonyl)hydrazine-1-carbothioamide (QST4), the most effective compound against Mycobacterium tuberculosis H37Rv, was also tested on isoniazid-resistant clinical isolates with katG and inhA promoter mutations. Based on molecular docking studies, QST4 was also likely to demonstrate its antimycobacterial activity through inhibition of the InhA enzyme. Furthermore, three derivatives (QST3, QST4, and QST10) with preferable antimicrobial and drug-like profiles were also shown to be nontoxic against human embryonic kidney (HEK) cells. All compounds were optimized by the density functional theory method using B3LYP with the 6-31+G(d,p) basis set. Structural analysis, natural bond orbital calculations of donor-acceptor interactions, molecular electrostatic potential analysis, and frontier molecular orbital analysis were carried out. Quantum chemical descriptors and charges on the atoms were determined to compare the strengths of the intramolecular hydrogen bonds formed and their stabilities. We determined that the sulfur atom forms a stronger intramolecular hydrogen bond than the nitrogen, oxygen, and fluorine atoms in these sulfonyl thiosemicarbazide derivatives.

A newly synthesized thiosemicarbazide derivative trigger apoptosis rather than necroptosis on HEPG2 cell line.

Thiosemicarbazide derivatives have been the focus of scientists owing to their broad biological activities such as anticancer, antimicrobial, and anti-inflammatory. Herein, we designed and synthesized a new thiosemicarbazide derivative (TS-1) and evaluated its antiproliferative potential against the human hepatocellular carcinoma cell line (HEPG2) and human umbilical vein endothelial cell line (ECV-304). Also, it was aimed to investigate the necroptotic and apoptotic cell death effects of TS-1 in HEPG2 cells, and these effects were supported by molecular docking. The new synthesized compound structure was characterized using various spectroscopic methods such as FT-IR, 1 H-NMR, 13 C-NMR, and elemental analysis. The cytotoxic activity of the tested compound was measured by the MTT assay. Apoptotic and necroptotic properties of the TS-1 were evaluated by indirect immunoperoxidase method using antibodies against Ki-67, Bax, Bcl-2, caspase-3, caspase-8, caspase-9, RIP3, and RIPK1. Apoptotic and necroptotic effects of TS-1 were supported by molecular docking. Compound TS-1 was synthesized as a pure compound with a high yield. The effective value of TS-1 was 10 μM in HEPG2 cells. TS-1 did not show any cytotoxic effect on ECV-304. Caspase-3 and RIPK1 immunoreactivities were significantly increased in HEPG2 cells after being treated with TS-1. As the results of the molecular docking studies, the molecular docking showed that the TS-1 exhibits H-bond interaction with various significant amino acid residues in the active site of both RIPK1. It could be concluded that TS-1 could be a promising novel therapeutic agent by inducing apoptosis rather than necroptosis in HEPG2 cells.

New Thiosemicarbazide Analogs as Antagonist of Nicotinic Muscarinic Receptors: Synthesis, In silico, and In vivo Screening

Some new thiosemicarbazide derivatives (5*a-5*b and 6a-6f) were synthesized by multiple steps approaches starting from substituted anilines. The synthesized compounds were evaluated for their muscle relaxant activity by an in silico docking study against nicotinic muscarinic receptor (protein database [PDB] ID: 2XNU) using AutoDock Vina and Biovia discovery studio tools. The rotarod test was also used to evaluate the muscle-relaxing activity of the compounds. The results were compared with generic diazepam to corroborate both research findings. In the in silico test, all the compounds showed 2–4 interactions with the target nicotinic muscarinic receptor (PDB ID- 2XNU) having binding affinities in the range of −5.8–−7.8 Kcal/mol. Among them, the 6a compound demonstrated the most remarkable relaxant activity with four hydrogen bond interactions with amino acids TYRC: 52, ILE C: 88, ALA C:90, and GLN C:119 of the target molecule. In addition, the rotarod test showed that compounds 5*a and 6d also had more muscle-relaxing effects than diazepam.

Synthesis and Diverse Pharmacological actions of Thiosemicarbazide Analogs: A Review

Background: Thiosemicarbazide is an important substance in the synthesis of pharmacological and bioactive substances, and it is commonly used in the discovery of new medications. Multiple synthetic approaches exist for the creation of different thiosemicarbazide analogs, which are then discovered to treat a variety of diseases. Objective: This review paper aims to determine the growing importance of thiosemicarbazide analogs in various types of sickness by examining various unique synthetic methods that have been described to manufacture them. Method: To incorporate published research and review papers, a comprehensive review of the literature from many sources during the past 24 years was conducted. Result: This paper summarises the findings of a literature review about the synthesis and biological activity of thiosemicarbazide and thiosemicarbazone derivatives. Conclusion: Numerous new studies on the role of thiosemicarbazide and thiosemicarbazone derivatives, as well as their methods of production and biological activity for various forms of the disease, are discussed in this review article.