Carbothioamide Derivatives Research Articles

Selective cyanide ion detection using hydrazine carbothioamide probe: A fluorescence turn-on approach

This study reports the synthesis of various hydrazine carbothioamide derivatives through a Schiff base reaction, confirmed by FT-IR, NMR (1H and 13C), and HRMS spectroscopic methods. Among the synthesized derivatives, probe L ((4-fluorobenzylidene)-2-(1-phenylethylidene)hydrazine-1-carbothioamide) was identified as a highly selective fluorometric chemosensor based on its absorbance and emission spectra. Probe L showed a CN− ion-specific turn-on fluorescence response, with very little interference from other anions. Job's method established a 1:1 binding stoichiometry among probe L and the cyanide ion. The detection limits (LOD) and quantification (LOQ) were observed to be 0.639 µM and 2.116 µM, respectively. With the use of FT-IR spectroscopy, 1H NMR titration, 13C NMR and HRMS, the binding mechanism was clarified. Moreover, probe L was employed effectively for detecting CN− ions in water and food samples, highlighting its potential as a practical sensor for cyanide detection.

Synthesis and Biological evalution of heterocyclic oxazine-2-carbonothioyl)quinazolin-4(3H)-one and oxazine-2(3H)-carbothioamide derivatives

An efficient route for the preparation of novel heterocyclic oxazine-carbonothioyl-quinazolin-(3H)-one and oxazine-(3H)-carbothioamide derivatives is through synthesis of 2-phenyl-4H-benzo[d][1,3] oxazin-4-one(anthranilic acid and benzoyl chlordide) which further reacts with thiourea and thiosemicarbazide to give substituted amines, which formed oxo-2-phenylquinazoline-3(4H)-carbothioa mide and oxo-2-phenylquinazolin-3(4H)-yl)thiourea (β-naphthol,substituted aromatic formedehyde). The structures of all the prepared derivatives were elucidated by using UV-Vis IR, 1HNMR and Mass spectral studies and antimicrobial activity in vitro was studied by serial dilution method. The newly prepared derivatives showed noticeable antimicrobial properties.

Discovery of Pyrazolone Carbothioamide Derivatives as Inhibitors of the Pdr1-KIX Interaction for Combinational Treatment of Azole-Resistant Candidiasis.

Candida glabrata has emerged as an important opportunistic pathogen of invasive candidiasis due to increasing drug resistance. Targeting Pdr1-KIX interactions with small molecules represents a potential strategy for treating drug-resistant candidiasis. However, effective Pdr1-KIX inhibitors are rather limited, hindering the validation of target druggability. Here, new Pdr1-KIX inhibitors were designed and assayed. Particularly, compound B8 possessed a new chemical scaffold and exhibited potent KIX binding affinity, leading to enhanced synergistic efficacy with fluconazole to treat resistant C. glabrata infection (FICI = 0.28). Compound B8 acted by inhibiting the efflux pump and down-regulating resistance-associated genes through blocking the Pdr1-KIX interaction. Compound B8 exhibited excellent in vitro and in vivo antifungal potency in combination with fluconazole against azole-resistant C. glabrata. It also had direct antifungal effect to treat C. glabrata infection, suggesting new mechanisms of action independent of Pdr1-KIX inhibition. Therefore, compound B8 represents a promising lead compound for antifungal drug development.

Exploring Novel Pyridine Carboxamide Derivatives as Urease Inhibitors: Synthesis, Molecular Docking, Kinetic Studies and ADME Profile.

The rapid development of resistance by ureolytic bacteria which are involved in various life-threatening conditions such as gastric and duodenal cancer has induced the need to develop a new line of therapy which has anti-urease activity. A series of pyridine carboxamide and carbothioamide derivatives which also have some novel structures were synthesized via condensation reaction and investigated against urease for their inhibitory action. Among the series, 5-chloropyridine-2 yl-methylene hydrazine carbothioamide (Rx-6) and pyridine 2-yl-methylene hydrazine carboxamide (Rx-7) IC50 = 1.07 ± 0.043 µM, 2.18 ± 0.058 µM both possessed significant activity. Furthermore, molecular docking and kinetic studies were performed for the most potent inhibitors to demonstrate the binding mode of the active pyridine carbothioamide with the enzyme urease and its mode of interaction. The ADME profile also showed that all the synthesized molecules present oral bioavailability and high GI absorption.

Synthesis, docking study, and structure activity relationship of novel anti-tumor 1, 2, 4 triazole derivatives incorporating 2-(2, 3- dimethyl aminobenzoic acid) moiety

A series of 1,2,4 triazole derivatives (H7-12) have been synthesized by reacting an excess of hydrazine hydrate with carbothioamide derivatives (H1-6). The final compounds (HB1-HB6) were synthesized by reacting the triazole derivatives with mefenamic acid using DCC as a coupling agent. The chemical structures were confirmed by FT-IR,1H, and13C-NMR spectra, and some physicochemical properties were determined. The cytotoxicity of the different compounds (HB1-HB6) was evaluated by the MTT assay against two human epithelial cancer cell lines, A549 lung carcinoma and Hep G2 hepatocyte carcinoma, and one normal human cell line WI-38 lung fibroblasts. The mode of cell killing (apoptosis versus necrosis), as well as the effect on cell cycle phases were evaluated via flow cytometry. Additionally, EGFR tyrosine kinase inhibition assay was performed. The results presented in the current study indicate that the six tested compounds exhibited cytotoxicity against both cancer cell lines, and the lowest IC50was achieved with compound HB5 against Hep G2 cancer cells which was found to be highly selective against cancer cells. HB5-treated Hep G2 cells were arrested at the S and G2/M cell cycle phases. Compound HB5 caused cell killing via apoptosis rather than necrosis, and this was achieved by inhibiting EGFR tyrosine kinase activity needed for cell proliferation, and cell cycle progression. In silicopre-ADMET studies confirmed all final compounds don’t cause CNS side effects, with little liver dysfunction effect.

Synthesis of Carboxamides and Carbothioamides of Phthalimide: Molecular Modeling and Biological Investigation

A series of carboxamide and carbothioamide derivatives of phthalimide have been synthesized efficiently by employing water as a green reaction media. The synthesized N-substituted phthalimide derivatives have been characterized by spectroscopic, elemental and their quantum parameters, including molecular orbital energies are deduced by DFT modeling. The molecular docking of synthesized derivatives against B-DNA (pdb:1bna) displays favourable binding interactions and satisfactory docking scores, predicting their significant antimicrobial efficacy. The synthesized phthalimide derivatives were screened for in vitro antimicrobial and antioxidant activity using broth microdilution method and DPPH radical scavenging assay, respectively. Some of the title compounds exhibited promising the antimicrobial and antioxidant potential. The pharmacokinetics parameters and bioavailability of the title compounds were accessed by in silico ADMET analysis to envisage their drug efficacy.

Solvent free synthesis of hydrazine carbothioamide derivatives as a precursor in the preparation of new mononuclear Mn(II), Cu(II), and Zn(II) complexes: Spectroscopic characterizations

ABSTRACT. Over the last few years considerable attention has been devoted to the study of Schiff base complexes of metal(II) containing nitrogen, oxygen and sulfur donor ligands due to their diverse biological activities. Therefore, the Schiff base thiosemicarbazone derivatives of 2-(2-hydroxy-3-methoxybenzylidene) hydrazine carbothioamide (HL1) and 2-(4-bromo-2-hydroxy-3-methoxybenzylidene) hydrazine carbothioamide (HL2) were synthesized with solvent free technique using silica gel as material support for the reaction. The structures of the precursor’s organic products confirmed with their 1H, 13C NMR, IR and microanalysis data. Six new manganese(II), copper(II), and zinc(II) complexes of HL1 and HL2 2-(2-hydroxy-3-methoxybenzylidene) hydrazinecarbothioamide derivatives with the general formulation [ML1Cl] and [ML2Cl], where M = Mn2+, Cu2+, and Zn2+ were prepared and well discussed by using elemental analyses, magnetic moments, molar conductance, infrared and electronic spectral techniques. The assignments data of spectroscopic analysis confirm that the synthesized thiosemicarbazone Schiff bases of acts as a tridentate ligand as sulfur-oxygen-nitrogen donating atoms. The values of magnetic moments agreed with the data of electronic spectra which both suggested a four-coordination geometry of the synthesized complexes.
 
 KEY WORDS: Schiff base, Thiosemicarbazone, Manganese(II) complex, Copper(II) complex, Zinc(II) complex
 
 Bull. Chem. Soc. Ethiop. 2021, 35(2), 413-424.
 DOI: https://dx.doi.org/10.4314/bcse.v35i2.14

Design, Synthesis, Spectroscopic Characterization of New Pyrazole Carbothioamides as Antifungal and Antibacterial Candidates

In a sustained search for novel antimicrobial agents as weaponry in the war against infectious diseases, resulting in improved survivability for both humans and their domestic animals, the present study demonstrates an efficient synthesis of N,N-dimethylaminophenyl substituted pyrazole carbothioamide derivatives. The synthesis involves (3+2) cycloaddition of chalcones with hydrazinecarbothioamide hydrochloride in the presence of the amberlyst-15 catalyzed at room temperature. The structures of new compounds were characterized by spectroscopic analysis. Furthermore, the synthesized new compounds 5(a-g) were assessed in vitro for their antimicrobial susceptibilities. The results indicate that compounds 5a found potent against tested bacteria species; 5b and 5c show excellent inhibition against the tested fungi and bacteria species. Therefore, these could act as antifungal and antibacterial leads for further investigations.

Functionalized Oxoindolin Hydrazine Carbothioamide Derivatives as Highly Potent Inhibitors of Nucleoside Triphosphate Diphosphohydrolases.

Ectonucleoside triphosphate diphosphohydrolases (NTPDases) are ectoenzymes that play an important role in the hydrolysis of nucleoside triphosphate and diphosphate to nucleoside monophosphate. NTPDase1, -2, -3 and -8 are the membrane bound members of this enzyme family that are responsible for regulating the levels of nucleotides in extracellular environment. However, the pathophysiological functions of these enzymes are not fully understood due to lack of potent and selective NTPDase inhibitors. Herein, a series of oxoindolin hydrazine carbothioamide derivatives is synthesized and screened for NTPDase inhibitory activity. Four compounds were identified as selective inhibitors of h-NTPDase1 having IC50 values in lower micromolar range, these include compounds 8b (IC50 = 0.29 ± 0.02 µM), 8e (IC50 = 0.15 ± 0.009 µM), 8f (IC50 = 0.24 ± 0.01 µM) and 8l (IC50 = 0.30 ± 0.03 µM). Similarly, compound 8k (IC50 = 0.16 ± 0.01 µM) was found to be a selective h-NTPDase2 inhibitor. In case of h-NTPDase3, most potent inhibitors were compounds 8c (IC50 = 0.19 ± 0.02 µM) and 8m (IC50 = 0.38 ± 0.03 µM). Since NTPDase3 has been reported to be associated with the regulation of insulin secretion, we evaluated our synthesized NTPDase3 inhibitors for their ability to stimulate insulin secretion in isolated mice islets. Promising results were obtained showing that compound 8m potently stimulated insulin secretion without affecting the NTPDase3 gene expression. Molecular docking studies of the most potent compounds were also carried out to rationalize binding site interactions. Hence, these compounds are useful tools to study the role of NTPDase3 in insulin secretion.

Synthesis, structural, spectral and antibacterial activity of 3,3a,4,5-tetrahydro-2H-benzo[g]indazole fused carbothioamide derivatives as antibacterial agents

The crystal, spectral characteristics and antibacterial activityof two benzo[g]indazole fused carbothioamide derivatives are explained in this study. The structural characterization of our compounds 3-(4-methylphenyl)-N-phenyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-2-carbothioamide (BICT) and 3‐(4‐methoxyphenyl)‐N‐(4‐nitrophenyl)‐ 3,3a,4,5-tetrahydro-2H-benzo[g]indazole-2-carbothioamide (MNPBICT) using SCXRD technique is reported. The crystal structures of our derivatives are substantiated with 1H, 13C NMR and FTIR spectral methods. For the synthesized compounds, in silico drug likeness screening using SwissADME online server and DNA gyrase inhibition activity through molecular docking studies (PDB ID: 1KZN) with bacterial protein are reported. The antibacterial activity of our compounds are tested against S. Aureus, B. megaterium, P. Aeroginosa and E. coli bacterial strains by disk broth dilution method. From the in silico pharmacological screening and docking results, it is found that our compound MNPBICT possess higher druggable nature and are effective DNA gyrase inhibitor against protein 1KZN compared to BICT and drug ciprofloxacin. The in vitro analysis explored the promising antibacterial activity of derivative MNPBICT and could be considered as a lead compounds for antibacterial drug design.

Synthesis and biological evaluation of (3/4-(pyrimidin-2-ylamino)benzoyl)-based hydrazine-1-carboxamide/carbothioamide derivatives as novel RXRα antagonists

Abnormal alterations in the expression and biological function of retinoid X receptor alpha (RXRα) have a key role in the development of cancer. Potential modulators of RXRα as anticancer agents are explored in growing numbers of studies. A series of (4/3-(pyrimidin-2-ylamino)benzoyl)hydrazine-1-carboxamide/carbothioamide derivatives are synthesised and evaluated for anticancer activity as RXRα antagonists in this study. Among all synthesised compounds, 6A shows strong antagonist activity (half maximal effective concentration (EC50) = 1.68 ± 0.22 µM), potent anti-proliferative activity against human cancer cell lines HepG2 and A549 cells (50% inhibition of cell viability (IC50) values < 10 µM), and low cytotoxic property in normal cells such as LO2 and MRC-5 cells (IC50 values > 100 µM). Further bioassays indicate that 6A inhibits 9-cis-RA-induced activity in a dose-dependent manner, and selectively binds to RXRα-=LΒD with submicromolar affinity (Kd = 1.20 × 10−7 M). 6A induces time-and dose-dependent cleavage of poly ADP-ribose polymerase, and significantly stimulates caspase-3 activity, leading to RXRα-dependent apoptosis. Finally, molecular docking studies predict the binding modes for RXRα-LBD and 6A.

Design, synthesis, molecular modelling and biological evaluation of novel 3-(2-naphthyl)-1-phenyl-1H-pyrazole derivatives as potent antioxidants and 15-Lipoxygenase inhibitors

Oxidative stress is one of the main causes of significant severe diseases. The discovery of new potent antioxidants with high efficiency and low toxicity is a great demand in the field of medicinal chemistry. Herein, we report the design, synthesis molecular modelling and biological evaluation of novel hybrids containing pyrazole, naphthalene and pyrazoline/isoxazoline moiety. Chalcones 2a–e were synthesized efficiently and were used as starting materials for synthesis of a variety of heterocycles. A novel series of pyrazoline 3a–e, phenylpyrazoline 4a–e, isoxazoline 5a–e and pyrazoline carbothioamide derivatives 6a–e were synthesized and screened for in vitro antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO) and superoxide radical scavenging assay as well as 15-lipoxygenase (15-LOX) inhibition activity. Compounds 3a, 4e, 5b, 5c, 6a, 6c, and 6e showed excellent radical scavenging activity in all three methods in comparison with ascorbic acid and 15-LOX inhibition potency using quercetin as standard then were subjected to in vivo study. Catalase (CAT) activity, glutathione (GSH) and malondialdehyde (MDA) levels were assayed in liver of treated rats. Compounds 5b, 5c, and 6e showed significant in vivo antioxidant potentials compared to control group at dose of 100 mg/kg B.W. Molecular docking of compound 6a endorsed its proper binding at the active site pocket of the human 15-LOX which explains its potent antioxidant activity in comparison with standard ascorbic acid.

Design, synthesis and pharmacological evaluation of carboxamide and carbothioamide derivatives of 1,3,4-thiadiazole as the inhibitors of acetylcholinesterase and oxipiperazine)ative stress for the management of cognitive debility

Acetylcholinesterase has been a promising target for the development of putative therapeutics against cognitive decline. The deleterious effect of oxidative stress on the learning and memory paradigms of an individual has also been well documented. In view of this and our previous findings on the ameliorative effects of amide derivatives of 1,3,4-thiaidiazoles on cognitive deterioration, the present study demonstrated the design, synthesis and pharmacological evaluation of carboxamides and carbothioamide derivatives of 1,3,4-thiadiazole. Novel carboxamide and carbothioamide derivatives were synthesised and characterised by various spectral and elemental techniques. Their effects on memory were studied by employing scopolamine induced amnesia in two behavioural animal models: Morris water maze and passive avoidance (dose of 0.5 mg/kg) with reference to the standard, Rivastigmine. In vitro AChE inhibition was studied at five different concentrations using the homogenised fraction of the decapitated mice brain as the source of the enzyme. Biochemical estimation of AChE, oxidative and nitrosative stress parameters have also been facilitated. Computational docking studies have been performed on human recombinant AChE (PDB ID: 4EY7) to assess the binding conformation of the molecules. The results indicated that the carbothioamide analogues 13a, 9b and 10b were found to be the most promising in the alleviation of cognitive decline induced by scopolamine. Among the carboxamide analogues, 8b has shown promising effect in the alleviation of cognition decline. Our results suggested the possible role of these derivatives in the mediation of cholinergic pathway and attenuation of oxidative stress resulting in the effective management of cognitive dysfunction.

Solid-state photochromic properties, mechanism and electrospun membranes of (E)-2-(benzo[b]thiophen-2-ylmethylene)-N-ethylhydrazine-1-carbothioamide

Three carbothioamide derivatives with reversible P-type photochromic properties in the solid state were synthesized in a one-step reaction. Based on the single crystal structures, the FT-IR spectra and theory calculations, the proposed photochromic mechanism was the intermolecular proton transfer between the thio-keto and thio-enol tautomer. Nanofibrous membranes were prepared by electrospinning, which showed improved reversible photochromic properties in comparison of the compound itself. This work may open a new pathway for design and synthesis of the new solid-state photochromic materials with high-performance.

Design and synthesis of some novel 7-substituted thiosemicarbazinyl-quinolines via Ullmann coupling reaction and examination of their antimicrobial activities

The present work demonstrates functionalization of 4,7-dichloro quinoline via a modified Ullmann coupling reaction concept of varying oxidation state and reaction conditions. Based on these conditions, novel 2-(4-morpholino quinolin-7-yl)-N-substituted phenyl hydrazinyl carbothioamide derivatives have been synthesized. Structures of the final synthesized compounds including intermediates were confirmed by IR, 1H NMR and 13C NMR spectral studies. Examination of biological profiles was carried out against various strains of micro-organisms. SAR and HOMO–LUMO calculations were carried out for judicious design.

Simple approach to thieno[3,2-d]pyrimidines as new scaffolds of antimicrobial activities.

6'-(4-Chlorophenyl)-spiro[cyclohexane-1,2'-thieno[3,2-d][1,3] oxazin]-4'(1'H)-one (1) was synthesized and used as a starting material for the synthesis of a novel series of spiro compounds having biologically active sulfonamide 2a-e and 3'-(4-acetylphenyl)-6'- (4-chlorophenyl)-1'H-spiro[cyclohexane-1,2'-thieno[3,2-d] pyrimidine-4'(3'H)-one (3). Compound 2a was used as a key intermediate for the synthesis of sulfonyl carbothioamide derivatives 4a-c. Also, compound 3 was used as an intermediate for the synthesis of 3'H-spiro[cyclohexane-1,2'-thieno[3,2-d]pyrimidin]-3'-yl] phenyl}-2-imino-4-(substituted phenyl and/or thienyl)-1,2-dihydropyridine- 3-carbonitrile derivatives 5a-e, 3'H-spiro[cyclohexane- 1,2'- thieno[3,2-d]pyrimidin]-3'-yl]phenyl}-2-oxo-4-(substituted phenyl and/or thienyl)-1,2-dihydropyridine-3-carbonitrile derivatives 6a-e, and 4-[(2Z)-3-substituted-arylprop-2-enoyl] phenyl-1'H-spiro[cyclohexane-1,2'-thieno[3,2-d]pyrimidine derivatives 7a-e. Cyclocondensation of 7a-e with hydrazine hydrate produced 6'-(4-chlorophenyl)-3'-[4-(5-substituted aryl-4,5-dihydro- 1H-pyrazol-3-yl)phenyl]-1'H-spiro[cyclohexane-1,2'-thieno- [3,2-d]pyrimidin]-4'(3'H)-ones 8a-e but with hydroxylamine hydrochloride afforded the corresponding isoxazoline derivatives 9a-e. Also, cyclocondensation by thiourea afforded 2-thioxo-1,2- dihydropyrimidin-4-yl)-phenyl-spiro-{cyclohexanethieno[3,2-d] pyrimidin}-4-one derivatives 10a-e. The new compounds were investigated for antimicrobial activity. Compounds 2c, 8b,c, 9b and 10b were the most potent ones against both Gram-negative and Gram-positive bacteria. Compound 8c exhibited higher antifungal activity towards the examined fungi with MIC of 1-2 μmol mL-1 compared to ketoconazole (MIC 2-3 μmol mL-1 ).

Synthesis, Antimicrobial and Hypoglycemic Activities of Novel N-(1-Adamantyl)carbothioamide Derivatives.

The reaction of 1-adamantyl isothiocyanate 4 with the various cyclic secondary amines yielded the corresponding N-(1-adamantyl)carbothioamides 5a–e, 6, 7, 8a–c and 9. Similarly, the reaction of 4 with piperazine and trans-2,5-dimethylpiperazine in 2:1 molar ratio yielded the corresponding N,N'-bis(1-adamantyl)piperazine-1,4-dicarbothioamides 10a and 10b, respectively. The reaction of N-(1-adamantyl)-4-ethoxycarbonylpiperidine-1-carbothioamide 8c with excess hydrazine hydrate yielded the target carbohydrazide 11, in addition to 4-(1-adamantyl)thiosemicarbazide 12 as a minor product. The reaction of the carbohydrazide 11 with methyl or phenyl isothiocyanate followed by heating in aqueous sodium hydroxide yielded the 1,2,4-triazole analogues 14a and 14b. The reaction of the carbohydrazide 11 with various aromatic aldehydes yielded the corresponding N'-arylideneamino derivatives 15a–g. The compounds 5a–e, 6, 7, 8a–c, 9, 10a, 10b, 14a, 14b and 15a–g were tested for in vitro antimicrobial activity against certain strains of pathogenic Gram-positive and Gram-negative bacteria and the yeast-like fungus Candida albicans. The compounds 5c, 5d, 5e, 6, 7, 10a, 10b, 15a, 15f and 15g showed potent antibacterial activity against one or more of the tested microorganisms. The oral hypoglycemic activity of compounds 5c, 6, 8b, 9, 14a and 15b was determined in streptozotocin (STZ)-induced diabetic rats. Compound 5c produced significant reduction of serum glucose levels, compared to gliclazide.

Synthesis and characterization of new 3,5-disubstituted-4,5-dihydro-1H-pyrazole and their carbothioamide derivatives

A new series of substituted pyrazolines (6-10) were synthesized in moderate to excellent yield by treatment of chalcones (1-5) with hydrazine monohydrate. The carbothioamide compounds (11-14) were obtained in 65% to quantitative yield by treatment of chalcones (2, 4, and 5) either with thiosemicarbazide or with phenylisothiocyanate. All new compounds were characterized by various spectroscopic methods such as 1 H NMR, 13 C NMR, DEPT, COSY, HSQC spectroscopy, elemental analysis, and high resolution mass spectroscopy. The obtained compounds are currently under biological investigations, and the results will be reported elsewhere.

Synthesis of novel N-aryl-4-[6-(2-fluoropyridin-3-yl)quinazolin-2-yl]-piperazine-1-carboxamide or -carbothioamide derivatives and their antimicrobial activity

Quinazolines are heterocyclic compounds with an important place in the field of medicinal chemistry. The quinazoline ring system is present in the structure of approximately 150 naturally occurring pharmacologically active alkaloids, isolated from a number of families of the plant and animal kingdom, as well as various microorga- nisms. 1 Quinazoline derivatives possess diverse biological and therapeutic activities such as antibacterial, 2-4 antifun- gal, 5 anti-inflammatory, 6 anticancer, 2,7 antituberculosis, 8 A series of novel N-aryl-4-(6-(2-fluoropyridin-3-yl)quinazolin-2-yl)-piperazine-1-carboxamide or -carbothioamide derivatives was synthe- sized by cyclization of 5-bromo-2-fluorobenzaldehyde and guanidine carbonate in the presence of dimethylacetamide followed by treatment with isoamylnitrite and diiodomethane in the presence of copper iodide to afford 6-bromo-2-iodoquinazoline. The latter was treated with piperazine in the presence of triethylamine followed by (2-fluoropyridin-3-yl)boronic acid in the presence of Pd(PPh3)2Cl2 to afford 6-(2-fluoropyridin-3-yl)-2-(piperazin-1-yl)quinazoline which was further treated with various substituted arylisocyanates and arylisothio- cyanates to obtain the title compounds. The chemical structures of the synthesized compounds were confirmed by means of LC-MS, 1 H, 13 C NMR, IR, and mass spectra and elemental analysis. All the synthesized compounds were evaluated for their in vitro antibacterial activity against two Gram-positive and two Gram-negative bacterial species, as well as two different strains of antibiotic-resistant E. coli and for antifungal activity against two fungal strains. Some of the compounds have shown potential antimicrobial activity.

Synthesis, spectral studies, in vitro and molecular docking studies of novel hydrazinyl carbothioamide derivatives

Five novel compounds possessing hydrazinyl carbothioamide moiety were designed and synthesized. All the compounds were tested for in vitro biological activities. Most of the tested compounds displayed strong antibacterial and antifungal activities. Molecular docking studies suggested that the hydrazinyl carbothioamide moiety of compounds (6–10) can in general be accommodated the binding pocket of the breast cancer protein (1JNX) and are responsible for the activity of the whole of the molecule. The docking results provide a new insight into the design of hydrazinyl carbothioamide derivatives as breast cancer drug.