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A series of novel tetralone/indanone moiety-bearing thiosemicarbazone derivatives were synthesized and evaluated for their biological activities. The structural elucidations of the compounds were performed by IR spectroscopy, 1H-NMR, 13C-NMR, and elemental analysis. Cytotoxic activity studies against A549 lung adenocarcinoma cells, CCD-19Lu fibroblast cell line were performed. Furthermore, flow cytometric analyses of mitochondrial membrane potential (JC1), caspase 3 activities, cytotoxic activities against HEK 293 immortalized human embriyonic kidney cell lines and MCF7 human breast cancer cell lines, COX-1 and COX-2 enzyme inhibition activities were evaluated for 2e, 2i, 3c, and 3d. In addition to the in vitro analysis, molecular docking studies were employed to explore the possible binding interactions of the title compounds with COX-1 (PDB ID: 3KK6) and COX-2 (PDB ID: 3LN1). Structure-activity relationships, as well as virtual ADME studies, were carried out and a relationship between the biological, electronic, and physicochemical qualifications of the target compounds was determined. Consequently, these derivatives present a leading structure for future drug development due to their straightforward synthesis and relevant bioactivity.

Objectives To synthesize and characterize 2-[[6-(4-bromophenyl)imidazo[2,1-b]thiazol-3-yl]acetyl]-N-alkyl/arylhydrazinecarbothioamide and 3-alkyl/aryl-2-[((6-(4-bromophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl)hydrazono]-5-nonsubstituted/methyl-4-thiazolidinone derivatives and evaluate them for their aldose reductase (AR) inhibitory effect. Materials and methods 2-[[6-(4-bromophenyl)imidazo[2,1-b]thiazol-3-yl]acetyl]-N-alkyl/arylhydrazinecarbothioamides (3a-f) and 3-alkyl/aryl-2-[((6-(4-bromophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl)hydrazono]-5-nonsubstituted/methyl-4-thiazolidinones (4a-j) were synthesized from 2-[6-(4-bromophenyl)imidazo[2,1-b]thiazole-3-yl]acetohydrazide (2). Their structures were elucidated by elemental analyses and spectroscopic data. The synthesized compounds were tested for their ability to inhibit rat kidney AR. Results Among the synthesized compounds, 2-[[6-(4-bromophenyl)imidazo[2,1-b]thiazol-3-yl]acetyl]-N-benzoylhydrazinecarbothioamide (3d) showed the best AR inhibitory activity. Conclusion The findings of this study indicate that the different derivatives of the compounds in this study may be considered interesting candidates for future research.

The purpose of this study was to synthesize imidazo[2,1-b] thiazole derivatives, characterize them with spectroscopical techniques and investigate for cytotoxic and apoptotic effects on glioma C6 cancer cell line. The in vitro anticancer activities were also investigated against focal adhesion kinase. Most of the compounds, particularly the derivatives carrying 3-oxo- 1- tiya- 4- azaspiro[ 4.5]decane moiety, exhibited higher or comparable activities in comparison with the reference drug, cisplatin. Compounds with methyl, propyl, phenyl moieties at the eighth and second position of the spirothiazolidinone ring showed high FAK inhibitory activities. In addition, molecular docking studies shed light on the binding modes of the synthesized compounds. The critical interactions with amino acid residues located in the active site were revealed. The results obtained from both biological assay data and computational results might provide insight into developing new inhibitors against focal adhesion kinase.

A series of novel oxo-hydrazone and spirocondensed-thiazolidine derivatives of imidazo[2,1-b]thiazole were synthesized and evaluated for their antioxidant activity. The antioxidant activity of 18 newly synthesized compounds and 12 previously reported compounds bearing similar scaffold, were evaluated by three different methods: inhibition of FeCl3/ascorbate system-induced lipid peroxidation of lecithin liposome (anti-LPO), scavenging activity against ABTS radical and Ferric Reducing Antioxidant Power (FRAP) activity. 4h, 5h, and 6h displayed the highest anti-LPO and ABTS radical removal activity. Also, in FRAP analysis, 4i and 4a displayed the best activity. In addition to the in vitro analysis, docking studies targeting the active site of Human peroxiredoxin 5 (PDB ID: 1HD2) were employed to explore the possible interactions of these compounds with the receptor. Structure-activity relationships, as well as virtual ADME studies, were carried out and a relationship between biological, electronic, and physicochemical qualifications of the target compounds was determined.

A series of novel indole-based hydrazide-hydrazone derivatives were synthesized and evaluated for their AChE and BuChE inhibitory activities. The structural elucidations of the novel compounds (2a–k) were performed by IR, 1H-NMR, 13C-NMR, mass, and elemental analysis. The inhibitory potential of the novel compounds on AChE (from electric eel) and BuChE (from equine serum) enzymes were carried out using in vitro modified Ellman's spectrophotometric method. Compounds 2f and 2d displayed the highest AChE inhibitory activity. Furthermore, 2d displayed the best BuChE inhibitory activity which was comparable with Galantamine. In addition to the in vitro analysis, docking studies targeting AChE (PDB ID: 1EVE ) and BuChE (PDB ID: 4BDS ) were performed to understand the possible interactions of these compounds with the enzymes. Structure-activity relationships, as well as in silico ADME studies, were performed and a relationship between biological, electronic, and physicochemical qualifications of the title compounds was determined.

Inhibiting the degradation of carbohydrates into glucose is considered to be an effective treatment for type 2 diabetes mellitus. Herein, a series of novel thiosemicarbazide and 1,2,4-triazole-3-thione derivatives of imidazo[2,1-b]thiazole were synthesized and evaluated for their α-glucosidase inhibitory activity. Compound 5c (IC50: 4.54 ± 0.19 µM) was found approximately 47 times more active than Acarbose (IC50: 214.71 ± 8.34 µM). In addition to the in vitro analysis, molecular docking studies were employed to explore the possible binding interactions of the title compounds. Structure-activity relationships, as well as virtual ADME studies, were carried out and a relationship between biological, electronic, and physicochemical qualifications of the target compounds was determined. Consequently, our studies indicated that these imidazo[2,1-b]thiazole derivatives possess the potential of being a novel class of α-glucosidase inhibitors.

Objectives The aim of this study was to determine the probable antibacterial, antitubercular, and antiviral activities of some N2 -arylidene-(6-(4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl) acetic acid hydrazides (3a-j). Further structural optimization of the identified lead structures can lead us to new more active potential antibacterial, antitubercular, and antiviral agents. Materials and methods Antibacterial activities of the title compounds against Staphylococcus aureus ATCC 29213, Pseudomonas aeruginosa ATCC 27853 and Escherichia coli ATCC 25922. These molecules were also evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv (ATCC 27294) using the BACTEC 460 radiometric system and BACTEC 12B medium. Moreover, all the compounds (3a-j) were also evaluated against some DNA and RNA viruses in Madin-Darby Canine Kidney, Crandell-Rees Feline Kidney (CRFK), Vero, human embryonic lung (HEL) and HeLa cells. Results Among the tested compounds, 3i displayed the highest efficacy against S. aureus and E. coli. Compound 3j, 5-nitro-2-furfurylidene derivative showed the highest antituberculosis activity (IC50: 6.16 µg/mL and IC90: 14.390 µg/mL). Compound 3i showed the most potent antiviral activity against feline corona virus in CRFK cell cultures (antiviral EC50: 7.5 µM and SI>13). Furthermore, compounds 3c and 3g displayed activity against herpes simplex virus-1 and vaccinia virus in HEL cell cultures (antiviral EC50 values of 9; 16 and 20; 14 µM, respectively). Conclusion On the basis of aforementioned results, it can be conluded that imidazo[2,1-b]thiazole derivatives bearing hydrazone moieties serve as promising chemical probes to design therapeutic agents with antibacterial, antitubercular, and antiviral properties.

Lately, much interest has been focused on the chemistry and the biological activity of fused heterocyclic compounds carrying nitrogen atoms because of their utility in various applications, and over the years N-bridged heterocyclic systems derived from 1,2,4-triazoles attracted the interest of researchers owing to the hopeful promise of their pharmacological activities such as antimicrobial, antifungal, molluscicidal, nematicidal, analgesic, anti-inflammatory, anticancer, phosphodiesterase 4 inhibitor, acetylcholinesterase, butyrylcholinesterases and alkaline phosphatase inhibitor. The fused ring of triazole and thiadiazines, named as triazolothiadiazines, represents a specific and important class of N-bridged heterocycles with their remarkable and wide range of biological activity and there are not enough studies that include the current developments associated with the new synthesis techniques and novel biological evaluation results of 1,2,4-triazolo[3,4-b][1,3,4] thiadiazine derivatives. In an attempt to overcome this deficiency in the literature, we deeply researched the literature and formed a review study about the discovery, synthesis and activity evaluation of new compounds bearing 1,2,4-triazolo[3,4-b][1,3,4]thiadiazine moiety within the years of 1996-2019. We aimed to provide scientists with a wide data resource about 1,2,4-triazolo[3,4-b][1,3,4]thiadiazine derivatives, thus helping them perform a more organized and fertile drug discovery operation during their experimental studies.

A series of arylidenehydrazide compounds (3a–3j) were synthesized from [6-(4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]acetic acid hydrazide. The newly synthesized compounds 3b and 3h were subjected to the National Cancer Institute’s in vitro disease-oriented antitumor screening to be evaluated for antitumor activity. Compound 3b, the most potent compound examined, displayed broad spectrum antiproliferative activity against all of the tested cell lines with log10GI50 values between −4.41 and −6.44. The greatest growth inhibitions were observed against an ovarian cancer cell line(OVCAR-3), a colon cancer cell line (HCT-15), two renal cancer cell lines (CAKI-1 and UO-31) and two leukemia cell lines (CCRF-CEM and SR) with log10GI10 values −6.44, −6.33, −6.11, −6.30, −6.13 and −6.22, respectively.

Graphical abstract, A novel series of indolylthiosemicarbazides (6a–6g) and their cyclization products, 4-thiazolidinones (7a–7g), have been designed, synthesized and evaluated, in vitro, for their antiviral activity against a wide range of DNA and RNA viruses. Compounds 6a, 6b, 6c and 6d exhibited notable antiviral activity against Coxsackie B4 virus, at EC50 values ranging from 0.4 to 2.1 μg/mL. The selectivity index (ratio of cytotoxic to antivirally effective concentration) values of these compounds were between 9 and 56. Besides, 6b, 6c and 6d also inhibited the replication of two other RNA viruses, Sindbis virus and respiratory syncytial virus, although these EC50 values were higher compared to those noted for Coxsackie B4 virus. The SAR analysis indicated that keeping the free thiosemicarbazide moiety is crucial to obtain this antiviral activity, since the cyclization products (7a–7g) did not produce any antiviral effect.

A series of novel thiosemicarbazide derivatives (2a-d) were synthesized from 3,5-bis(trifluoromethyl) benzohydrazide (1) and various substituted isothiocyanates. The structures of novel compounds were determined by analytical and spectral (IR, 1H-NMR, and elemental analysis) methods. In silico studies were conducted to determine and evaluate the potential anticancer activity of the compounds. Target-oriented drug design is crucial for cancer therapy for increasing the selectivity and consequently decreasing the adverse effects of anticancer agents. Computer-aided drug design technology enables us to design and develop target-oriented and hence, selective therapeutic agents. We benefited that technology during our drug design process and selected our targets as ATP-dependent enzyme topoisomerase II (Topo II), epidermal growth factor receptor (EGFR) tyrosine kinase domain, carbonic anhydrase IX and tubulin-colchicine: stathmin-like domain complex, which has significant roles in the cancer development process by their biochemical and physiological activities. In the light of the results obtained from in silico studies, the title compounds displayed significant potential activity about possessing the qualification of being multi-target drugs by effecting and hitting a few of the main targets of cancer chemotherapy together and at the same time. [Med-Science 2020; 9(2.000): 305-13]

Graphical abstract, Highlights • Development of novel antimycobacterial drugs is an obligation. • Spirothiazolidinone moiety is potent for antitubercular activity. • Ring closure of acyl-hydrazone derivatives increases antitubercular activity., A series of novel acyl-hydrazone (4a-d) and spirothiazolidinone (5a-d, 6a-d) derivatives of imidazo[2,1-b]thiazole were synthesized and evaluated for their antiviral and antimycobacterial activity. The antituberculosis activity was evaluated by using the Microplate Alamar Blue Assay and the antiviral activity was evaluated against diverse viruses in mammalian cell cultures. According to the biological activity studies of the compounds, 5a-c displayed hope promising antitubercular activity, 6d was found as potent for Coxsackie B4 virus, 5d was found as effective against Feline corona and Feline herpes viruses. Consequently, the obtained results displayed that, 5a-d and 6d present a leading structure for future drug development due to its straightforward synthesis and relevant bioactivity.

Objectives: To synthesize and characterize 2-[[6-(4-bromophenyl)imidazo[2,1-b]thiazol-3-yl]acetyl]-N-alkyl/arylhydrazinecarbothioamide and 3-alkyl/aryl-2-[((6-(4-bromophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl)hydrazono]-5-nonsubstituted/methyl-4-thiazolidinone derivatives and evaluate them for their aldose reductase (AR) inhibitory effect. Materials and Methods: 2-[[6-(4-bromophenyl)imidazo[2,1-b]thiazol-3-yl]acetyl]-N-alkyl/arylhydrazinecarbothioamides (3a-f) and 3-alkyl/aryl-2-[((6-(4-bromophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl)hydrazono]-5-nonsubstituted/methyl-4-thiazolidinones (4a-j) were synthesized from 2-[6-(4-bromophenyl)imidazo[2,1-b]thiazole-3-yl]acetohydrazide (2). Their structures were elucidated by elemental analyses and spectroscopic data. The synthesized compounds were tested for their ability to inhibit rat kidney AR. Results: Among the synthesized compounds, 2-[[6-(4-bromophenyl)imidazo[2,1-b]thiazol-3-yl]acetyl]-N-benzoylhydrazinecarbothioamide (3d) showed the best AR inhibitory activity. Conclusion: The findings of this study indicate that the different derivatives of the compounds in this study may be considered interesting candidates for future research.

The title compound, C19H19N5O3S2, crystallizes in the triclinic space groupP-1, with two independent molecules (AandB) in the asymmetric unit (Z′ = 2). The imidazo[2,1-b][1,3]thiazole ring systems in moleculesAandBare essentially planar (r.m.s deviations = 0.004 and 0.005 Å, respectively), with dihedral angles of 1.1 (3) and 0.8 (3)°, respectively, between the thiazole and imidazole rings. The mean planes of these ring systems make dihedral angles of 16.0 (2) and 61.9 (2)° for moleculeA, and 11.8 (2) and 74.3 (2)° for moleculeB, with the 1,3-thiazolidine and methoxy-substituted benzene rings, respectively. In the crystal, molecules are linkedviaN—H...O hydrogen bonds, forming –A–B–A–B– chains along [100]. The chains are linked by C—H...O hydrogen bonds, forming layers parallel to theabplane.

Objectives: The aim of this study was to determine the probable antibacterial, antitubercular, and antiviral activities of some N2-arylidene-(6-(4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl) acetic acid hydrazides (3a-j). Further structural optimization of the identified lead structures can lead us to new more active potential antibacterial, antitubercular, and antiviral agents. Materials and Methods: Antibacterial activities of the title compounds against Staphylococcus aureus ATCC 29213, Pseudomonas aeruginosa ATCC 27853 and Escherichia coli ATCC 25922. These molecules were also evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv (ATCC 27294) using the BACTEC 460 radiometric system and BACTEC 12B medium. Moreover, all the compounds (3a-j) were also evaluated against some DNA and RNA viruses in Madin-Darby Canine Kidney, Crandell-Rees Feline Kidney (CRFK), Vero, human embryonic lung (HEL) and HeLa cells. Results: Among the tested compounds, 3i displayed the highest efficacy against S. aureus and E. coli. Compound 3j, 5-nitro-2-furfurylidene derivative showed the highest antituberculosis activity (IC50: 6.16 µg/mL and IC90: 14.390 µg/mL). Compound 3i showed the most potent antiviral activity against feline corona virus in CRFK cell cultures (antiviral EC50: 7.5 µM and SI>13). Furthermore, compounds 3c and 3g displayed activity against herpes simplex virus-1 and vaccinia virus in HEL cell cultures (antiviral EC50 values of 9; 16 and 20; 14 µM, respectively). Conclusion: On the basis of aforementioned results, it can be conluded that imidazo[2,1-b]thiazole derivatives bearing hydrazone moieties serve as promising chemical probes to design therapeutic agents with antibacterial, antitubercular, and antiviral properties.

A series of 4-alkyl/aryl-2,4-dihydro-5-((6-(4-bromophenyl)imidazo[2,1- b ]thiazol-3-yl)methyl)-3 H -1,2,4-triazole-3-thiones ( 3a – i ) and 2-alkyl/arylamino-5-((6-(4-bromophenyl)imidazo[2,1- b ]thiazol-3-yl)methyl)-1,3,4-thiadiazoles ( 4a – c ) were synthesized starting from 6-(4-bromophenyl)imidazo[2,1- b ]thiazole-3-acetic acid hydrazide. The newly synthesized compounds were characterized by IR, 1 H NMR, mass and elemental analysis. All compounds were tested for antibacterial and antifungal activities. The antimicrobial activities of the compounds were assessed by the microbroth dilution technique. The compounds were also evaluated for antituberculosis activity against Mycobacterium tuberculosis H 37 Rv (ATCC 27294). The preliminary results revealed that some of the compounds exhibited promising antimicrobial activities.

In this work, we reported the synthesis and evaluation of antibacterial and antifungal activities of three new compound series obtained from 6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazole-3-acetic acid hydrazide: 2-{[6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]acetyl}-N-alkyl/arylhydrazinecarbothioamides (2a-d), 4-alkyl/aryl-2,4-dihydro-5-{[6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]methyl}-3H-1,2,4-triazole-3-thiones (3a-n), and 2-alkyl/arylamino-5-{[6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]methyl}-1,3,4-thiadiazoles (4a-g). The newly synthesized compounds were characterized by IR, (1)H NMR, (13)C NMR (APT), mass and elemental analysis. Their antibacterial and antifungal activities were evaluated against Staphylococcus aureus ATCC 29213, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, Candida albicans ATCC 10231, C. parapsilosis ATCC 22019, C. krusei ATCC 6258, Trichophyton mentagrophytes var. erinacei NCPF 375, Microsporum gypseum NCPF 580, and T. tonsurans NCPF 245. 3c, 3f, 3m, 3n, and 4e showed the highest antibacterial activity. Particularly 3c, 3f, 3g, 3k, 3n, 4a, 4e, and 4g showed the highest antifungal activity against tested fungi.

In the title compound, C28H27BrN4O3S2·2C2H6O, the cyclohexane ring adopts a chair conformation. The imidazo[2,1-b][1,3]thiazole ring system is essentially planar with a dihedral angle of 1.1 (2)° between the thiazole and imidazole rings. The mean plane of this ring system makes dihedral angles of 8.11 (16) and 79.43 (17)°, respectively, with the bromo- and hydroxy-substituted benzene rings. In the 5-methyl-1,3-thiazolidin-4-one group, the S atom, the methyl group and the ring C atoms bonded to them are disordered over two sets of sites with refined occupancies of 0.610 (19) and 0.390 (19). The crystal structure features N—H...O, O—H...O, O—H...N and C—H...O hydrogen bonds and C—H...π interactions. Furthermore, two weak π–π stacking interactions [centroid–centroid distances = 3.967 (3) and 3.892 (2) Å] are also observed.

New 4-thiazolidinone derivatives of benzilic acid (alpha,alpha-diphenyl-alpha-hydroxyacetic acid) have been synthesized and evaluated for antibacterial and antifungal activities. The reaction of 1- (alpha,alpha-diphenyl-alpha-hydroxy)acetyl-4-alkyl/arylthiosemicarbazides with ethyl 2-bromopropionate gave 3-alkyl/aryl-2-[((alpha,alpha-diphenyl-alpha-hydroxy)acetyl)hydrazono]-5-methyl-4-thiazolidinone derivatives. Their antibacterial and antifungal activities were evaluated against S. aureus ATCC 29213, P. aeruginosa ATCC 27853, E. coli ATCC 25922, C. albicans ATCC 10231, C. parapsilosis ATCC 22019, C. krusei ATCC 6258, T. mentagrophytes var. erinacei NCPF 375, M. gypseum NCPF 580 and T. tonsurans NCPF 245. 3e, 3f, 3g and 3h showed the highest antibacterial activity. Particularly 3a and 3e showed the highest antifungal activities against C. parapsilosis ATCC 22019, T. tonsurans NCPF 245 and M. gypseum NCPF 580.

WOS: 000248149900244 In the title compound, C18H19BrN4OS, the thiazole and imidazole rings make a dihedral angle of 0.7 (2)degrees with each other. The dihedral angle between the benzene ring and the mean plane of the fused rings is 2.99 (15)degrees. The crystal structure is stabilized by intermolecular N - H...O hydrogen bonds and possible C - H...O interactions.

WOS: 000255450100141 PubMed: 21202301 The title compound, C21H22N4O2S2 center dot 0.5H(2)O,crystallizes with two molecules in the asymmetric unit. The dihedral angles between the phenyl and imidazothiazole ring systems are 19.16 (9) and 21.37 (9)degrees. In the imidazothiazole ring systems, the cyclohexane rings adopt chair conformations, while the thiazole rings have distorted envelope conformations. The two molecules are stabilized by intramolecular N-H center dot center dot center dot O, O-H center dot center dot center dot O and C-H center dot center dot center dot S interactions and the crystal structure is stabilized by intermolecular N-H center dot center dot center dot O, O-H center dot center dot center dot O, C-H center dot center dot center dot O and C-H center dot center dot center dot N interactions.