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New hybrids of 4-aminothiazolo-2-quinolone-5-carbonitriles were synthesized and assessed for their antiproliferative activity against lung and colon cancer cell lines (A549 and Caco-2, respectively) in addition to normal human cells (WI-38) using MTT assay and sorafenib as reference drug. Five derivatives exhibited high potency and selectivity for A549 cancer cells. The active candidates promoted apoptosis of lung cancer cells through expression of Bax, Bcl-2, p53, EGFR, PI3K, and mTOR signaling pathway as suggested by RT-PCR data. Moreover, in vitro enzymatic inhibition assays of epidermal growth factor receptor (EGFR) and phosphoinositol 3-kinase (PI3K) were performed. A 6-methoxy-2-quinolone derivative demonstrated inhibition of EGFR comparable to that of gefitinib while a 1-ethyl-2-dihydroquinolone derivative showed significant inhibition to PI3K higher than buparlisib. [ABSTRACT FROM AUTHOR]

A series of {1-[4-(4-chlorophenyl)-1,3-thiazol-2-yl]-1H-pyrazol-4-yl}(2-hydroxyphenyl)metha-nones 5 were synthesized from 1-[4-(4-chlorophenyl)-1,3-thiazol-2-yl]hydrazine 3 and substituted 3-formyl-chromones 4. Compounds 5 were converted into 2-[(E)-{1-[4-(4-chlorophenyl)-1,3-thiazol-2-yl]-1H-pyrazol-4-yl}(hydroxyimino)methyl]phenols 6. The synthesized compounds were characterized by spectral techniques screened for their anti-inflammatory activity. Compounds 6c and 6e showed good percent inhibition of haemolysis when compared with the standard drug celecoxib. The molecular docking study explored the essential binding mode and possible thermodynamic interactions within the binding site of COX-2 enzyme. [ABSTRACT FROM AUTHOR]

In this study, we have investigated a strategy for designing some novel pyrazoline-thiazole hybrids containing azo moiety. The synthesized compounds were structurally characterized and their antibacterial activity was in vitro evaluated against gram-negative and gram-positive bacteria using the inhibition zone method. The antibacterial activity of the tested compounds was moderate to good. Compound 12c showed the best activity compared to the standard drug (Ampicillin) against S. aureus and E. coli at the concentration of 0.16 mg/mL, with the highest inhibition zone diameters of 34 mm and 37 mm, respectively. Moreover, in silico molecular docking and ADME profile studies were investigated in order to understand the binding affinity and interactions along with the ADME properties of all designed hybrids. Additionally, Density functional theory (DFT) calculations were carried out at the B3LYP/6-311G++ level of theory. The study involved an examination of the optimized geometry, molecular electrostatic potential map, and the HOMO → LUMO electronic energy gap. In accordance with the findings, the newly synthesized hybrids could be beneficial for medicine and exhibit antibacterial activity. [ABSTRACT FROM AUTHOR]

Objective: The "fall armyworm" also known as Spodoptera frugiperda, is a maize pest that is native to North America. It invaded Africa in 2016 and caused serious economic damage, forcing the continent's nations to take swift action to fend off this new invading pest. It is urgently necessary to produce powerful insecticides for the efficient management of this insect pest since this parasite is a novel invading species and its resistance to insecticides has to be investigated. Methods: The synthesized thiazole-owing hydrazone derivatives are the subject of the first study on the harmful effects they cause, followed by structural relationships. Following the stated protocols, four molecules of thiazole-owing hydrazone derivatives were synthesized as pure active ingredients, and their efficacy as potential insecticides against S. frugiperda was tested. Results and Discussion: The toxicity data exhibited that compound (V) with LC50 of 13.66 and 106.25 ppm was more toxic against the 2nd and 4th larvae instars, respectively, than other synthesized compounds; the other screened compounds showed weak to strong toxicological activity against S. frugiperda. A molecular docking investigation of four synthetic compounds (III–VI) was performed against acetylcholinesterase (AChE). The molecular docking results revealed that compound (V) has the more negative docking score and best binding (docking score = –9.01 kcal/mol), followed by compounds (III), (IV), and (VI) with docking scores of –8.76, –8.53, and –7.41 kcal/mol, respectively. The protein-ligand docking postures revealed that these substances exhibited a strong affinity for the target enzyme's active site (Protein Data Bank ID: 2ACE). This work suggests that these substances may have insecticidal and AChE inhibitory properties, and it may be possible to further explore them in the process of creating pesticides that target AChE. [ABSTRACT FROM AUTHOR]

A general and sustainable approach for the synthesis of benzimidazole-thiazole compounds via an efficient, one-pot, domino, pseudo-four-component reaction using 5-amino-2-mercaptobenzimidazole, aralkyl halides, ammonium thiocyanate, and substituted α-bromo-acetophenones in glacial acetic acid at ambient temperature to give final compounds (4a–p) in good yields in shorter time. The spectral data of synthesized compounds were evaluated by analytical and spectral techniques (IR, 1H-NMR, 13C-NMR, and ESI-HRMS). Further, some of the synthesized compounds were screened for their in-vitro antibacterial activity studies using the agar well diffusion method against Gram-positive Streptococcus pneumoniae (2451) bacteria and Gram-negative Proteous mirabilis (2081) bacteria. Based on the MIC results, it was observed that the most active compounds 4b, 4e, 4f, and 4k show promising antibacterial activity with the zone of inhibition values of 2.85 cm 2.75 cm, 3.6 cm, and 3.3 cm against both Gram-negative and positive bacteria cell lines, respectively. Further, we have also insight into the molecular simulation studies, based on the binding results, compound 4i showed stable binding interactions with streptomycin drug with the active site of the gyrase protein (PDB ID: 1KIJ). The structure–activity relationship (SAR) studies of all the title scaffolds were also established. The antibacterial activity, molecular docking studies, and molecular dynamic simulations of the title compounds suggested that these are promising antibacterial active skeletons. [ABSTRACT FROM AUTHOR]

In this study, we present a series of 2-(5-chlorothiophen-2-yl)-1H-benzo-[d]-imidazol-2-yl)-6,7-dihydrobenzo-[d]-imidazo[2,1-b]thiazol-8(5H)-ones (7a–q) through a short, four-step process using readily available starting materials. The synthesis included crucial transformations such as the condensation of 1,3-cyclohexanediones with thiourea, cyclization with acetophenones, and the Vilsmeier-Haack-Arnold reaction. All the compounds were fully characterized and systematically screened for antibacterial, antifungal and antiviral activity. Among all, the compounds 7b (CC50: >1000 µM, IC50 = 4.8 µM, SI = > 63) and 7h (CC50: >1000 µM, IC50 = 5.6 µM, SI = > 54) with 3-methyl and 3-trifluoromethyl groups showed significant virus inhibitory activity against the pandemic influenza virus A/Puerto Rico/8/34 (H1N1) with high selectivity index values and favorable toxicity profiles. The compounds were also evaluated for antibacterial and antifungal activity, exhibited only moderate inhibition. Molecular docking studies have elucidated strong binding interactions with the viral target, the RNA polymerase PB1-PB2 subunits of influenza A virus. ADMET profiles highlighted encouraging drug-like properties and positioned 2-(5-chlorothiophen-2-yl)-1H-benzo-[d]-imidazol-2-yl)-6,7-dihydrobenzo-[d]-imidazo [2,1-b]thiazol-8(5H)-one as a promising candidate for further development as antiviral therapeutics. [ABSTRACT FROM AUTHOR]

In an attempt to search for new natural product-based antitumor agents, a series of novel thiazolidinone derivatives of dehydroabietic acid-based B ring-fused-thiazole were designed and synthesized. The primary antitumor tests showed that compounds 5 m exhibited almost the best inhibitory activity against the tested cancer cells. The computational study suggested NOTCH1, IGF1R, TLR4, and KDR were the core targets of the title compounds, and the IC50 of SCC9 and Cal27 is strong correlation with the binding ability of TLR4 and compounds. [ABSTRACT FROM AUTHOR]

Various sets of thiazole, thiophene, and 2-pyridone ring structures containing a dimethylaniline component were synthesized. Substituted thiazoles 2–3 and thiophenes 5–7 were produced by reacting thiocarbamoyl compound 4 with α-halogenated reagents in different basic conditions. Also, a series of 2-pyridone derivatives 9a–f substituted with dimethylaniline was synthesized through Michael addition of malononitrile to α,β-unsaturated nitrile derivatives 8a–f. The synthesized products were structurally proven by spectroscopic methods such as IR, 1H NMR, 13C NMR, and MS data. Furthermore, the anti-cancer efficacy of the compounds was assessed using the MTT assay on two cell lines: hepatocellular carcinoma (HepG-2) and breast cancer (MDA-MB-231). The results showed the highest growth inhibition for derivatives 2, 6, 7, and 9c, which were further examined for their IC50 values. The IC50 for compound 2 showed equipotent activity (IC50 = 1.2 µM) against the HepG-2 cell line compared to Doxorubicin (IC50 = 1.1 µM). Compounds 2, 6, 7 and 9c showed very good ADME assessments for further drug administration. Moreover, the PASS theoretical prediction for the compounds showed high antimitotic and antineoplastic activities for compounds 2, 6, 7, and 9c, as well as potent inhibition activity for the insulysin enzyme (IDE). Molecular docking stimulations were performed on CDK1/CyclinB1/CKS2 (PDB ID: 4y72) and BPTI (PDB ID: 2ra3). When docked into (PDB ID: 4y72), all of the tested compounds showed considerable inhibition, and the 2-pyridone derivative 9d had the maximum binding affinity (− 8.1223 kcal/mol). While thiophene derivative 6 offered the maximum binding affinity (− 7.5094 kcal/mol) when docked into (PDB ID: 2ra3). [ABSTRACT FROM AUTHOR]

Several novel approaches to target Bcl-2 proteins and apoptotic pathways have been identified in recent years for the treatment of different types of cancer including colorectal cancer. However, no effective treatments were yet developed for colorectal cancer. Twenty two novel benzoxazole and thiazole−based compounds were designed, synthesized, and evaluated as potential Bcl-2 inhibitors with anti−proliferative activity. Compounds 8g, 12e and 13d showed good to moderate anti−proliferative activity against most of the NCI 60 cell line panel with mean growth inhibition percent of 45.13, 42.29 and 29.25%, respectively. They showed the greatest cell growth inhibition percent to HCT-116 cell line with the values of 68.0, 59.11 and 43.44%, respectively. The aforementioned compounds were furtherly investigated for their effect on HCT-116 cell cycle, and they showed increase in the total apoptosis with 17, 22, and 5%, respectively. Also, the apoptotic effect of compounds 8g, 12e and 13d, were tested by their effect on altering caspase-3 expression level in HCT-116 human cell line. The three compounds showed an increase in the caspase-3 levels by 6, 8 and 3 folds, respectively in comparison with the same untreated ones. Moreover, they were evaluated for their in–vitro Bcl-2 inhibitory activity and they showed percent inhibition of 60.2, 69.2 and 50.0%, respectively. Finally, the most potent compounds 8g and 12e showed 3.864 and 2.834 folds increase in Bax level compared to the control respectively. On the other hand, Bcl-2 was down−regulated to 0.31 and 0.415 folds compared to the control. The induction of apoptosis through increase in caspase 3 expression and down−regulation of Bcl-2 is the suggested mechanism of action. [ABSTRACT FROM AUTHOR]

A facile one pot multi-component synthesis of novel 1,3,4-thiadiazine and thiazole derivatives from the reaction of (methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethan-1-one, thiocarbohydrazide/or thiosemicarbazide, and aromatic aldehydes. The synthesized compounds were evaluated for antimicrobial, antibiofilm, and antioxidant activity. The results revealed the marked potency as antimicrobial agents. Thiazole 6e has the highest antimicrobial activity. Furthermore, most compounds inhibited biofilms produced by Pseudomonas aeruginosa. Promising thiazole 6c and thiadiazine derivatives (4c and 4 g) exhibited superior antioxidant activity and remarkable scavenging activity with DPPH, (86.99 ± 1.1, 81.54 ± 3.4 and 78.25 ± 1.8) and ABTS (80.06 ± 0.12, 62.29 ± 0.31 and 44.38 ± 0.20) respectively. The molecular docking simulation showed lower binding energy with different types of interaction at the active site of Dihydropteroate synthase, Sortase A, LasR, and Penicillin-binding proteins pockets indicating that these compounds could inhibit the enzyme and cause promising antimicrobial effects. Also, Molecular docking to the active sites of Peroxidase enzyme as an antioxidant receptor revealed that thiadiazine derivatives (4c and 4d) displayed minimal binding energy and have a good affinity toward the active pocket of each enzyme. [ABSTRACT FROM AUTHOR]

In this study, the synthesis of the planned compounds was carried out in two steps. In the first step, 1-methylimidazole-2-carbaldehyde compound was reacted with thiosemicarbazide and thiosemicarbazone compound was obtained. In the second step, the thiosemicarbazone compound obtained in the first step was reacted with 2-bromoacetophenone derivative compounds and thiazole derivative compounds were obtained. The structures of the synthesized compounds were confirmed by 13C NMR, 1H NMR and HRMS spectral findings, and the melting point was determined for these compounds. The % inhibition values of the compounds on the enzyme acetylcholinesterase (AChE) and butyrylcholinesterase (BuCHe) were investigated. [ABSTRACT FROM AUTHOR]

In this work, 1-(4-(3-methyl-3-phenylcyclobutyl)thiazol-2-yl)-3-(p-tolyl)thiourea was synthesized by alcohol-mediated condensation of 4-(3-methyl-3-phenylcyclobutyl)thiazol-2-amine and isothiocyanatobenzene. The molecule results were experimentally characterized using FT-IR, 1H NMR, and 13C NMR spectroscopy. Density functional theory (B3LYP/6-311G) was used to investigate the ideal molecule structure, vibrational frequencies, and 1H with 13C NMR (theoretically) chemical shifts. Theoretical and experimental spectroscopy results were compared and agreed with each other, which indicated the validity of the used developed molecular structure. The Dipole moment, hardness, softness, electronegativity, electrophilicity index, nucleophilicity index, and chemical potential as electronic structural parameters linked to corrosion inhibition efficacy were investigated for the prepared compound. Furthermore, the fraction of transferred electrons was calculated to determine the interaction between the iron surface and organic molecules. The results indicated a favorable relationship between organic-based corrosion inhibitors and quantum chemical parameters processes. The corrosion inhibitors' behavior can be predicted without the need for experimental investigation. [ABSTRACT FROM AUTHOR]

Previously unknown hybrid compounds comprising a thiazole and a triazole moieties were synthesized with excellent yields and characterized by IR and NMR spectroscopy, mass spectrometry, and elemental analysis. The antibacterial activity of the produced hybrid compounds was tested against bacterial (E.coli, S.aureus) and fungal (C.albicans, A.niger) strains, and the minimal inhibitory concentrations were calculated. The majority of the newly synthesized hybrids showed a moderate to an excellent antibacterial activity. [ABSTRACT FROM AUTHOR]

A series of novel ethyl (Z)-2-cyano-3-[(4-methyl-5-{2-[(Z)-1-arylethylidene]hydrazine-1-carbonyl}thiazol-2-yl)amino]-3-(methylthio)acrylate derivatives was synthesized through four step method. The process generates novel thiazole derivatives in good yield, using low-cost, readily available chemicals with simple reaction conditions. Antimicrobial screening of desired synthesized molecules was tested against various bacteria and fungi. It was discovered that among all tested molecules, methoxy derivative and nitro derivatives exhibited a good activity against E. coli, P. aeruginosa and chloro, hydroxy, and nitro derivatives exhibited an excellent activity against A. niger, A. clavatus. Molecular docking study of synthesized molecules was performed on E. coli dihydropteroate synthase using the Auto Dock technique. An analysis of their physicochemical and pharmacokinetic properties related to ADMET was also carried out. [ABSTRACT FROM AUTHOR]

To alleviate the fire hazard of epoxy resin (EP), an efficient flame retardant (ADM) containing phosphophenanthrene and thiazole groups is synthesized and used as co-curing agent for 4,4′-diaminodiphenyl methane to prepare EP/ADM composites. EP/4 mass% ADM composites with phosphorus content of only 0.25 mass% reach UL-94 V-0 rating and the limiting oxygen index value is high to 35.8%. The results reveal that the peak heat release rate, total smoke production, and total heat release of EP/4 mass% ADM composites are reduced by 24%, 14.4% and 16.7%, respectively, in comparison with those of pure EP. The improvement in flame retardancy is mainly attributed to the decomposition of DOPO which produces HPO• and PO• to capture the reactive radicals in the gaseous phase. The thiazole group releases hindered amine groups and inactive gas with a dilution effect in the gaseous phase thus further enhancing the effect of the phosphophenanthrene group. Besides, ADM helps to increase the glass transition temperature (Tg) of EP/ADM composites, which is 176 °C for EP/4 mass% ADM composites, which is higher than the value (172 °C) of EP. [ABSTRACT FROM AUTHOR]

An effective one-pot three-component protocol for the synthesis of polysubstituted thiazole derivatives is reported. The reaction proceeds between arylglyoxals, thiosemicarbazones, and acetylacetone or ethyl acetoacetate in ethanol as solvent and in the presence of acetic acid as catalyst. [ABSTRACT FROM AUTHOR]

New series of biologically active triazole and pyrazole compounds containing 2, 4-disubstituted thiazole analogues (12a-l) were synthesized from p-hydroxy benzaldehyde and phenyl hydrazine in excellent yields and purity. All the synthesized compounds were unambiguously identified based on their spectral data analyses (IR, 1H-NMR, 13C-NMR spectra, and HRMS). The final derivatives were evaluated for their in vitro anti-microbial activity after thorough purification. Among all the tested compounds, the compound 12e, 12f and 12 k possess the highest growth inhibitory activity at MIC values of 4.8, 5.1 and 4.0 μg/ml respectively. The antioxidant properties of these compounds demonstrated and revealed remarkable activity compared to the standard antioxidant by using the DPPH free radical-scavenging assay. Moreover, molecular docking studies to evaluate the probable interactions with the catalytic domain of the gram-positive S. aureus topoisomerase IV enzyme may provide new insights for developing these new hybrids as potential antimicrobial agents. The binding affinities of compounds 12a-l were ranging from − 10.0 to − 11.0 kcal/mol with topoisomerase IV enzyme and with COVID-19 main protease binding affinities are ranging from − 8.2 to − 9.3 kcal/mol. These docking studies reveal that the compounds 12a-l could be the best inhibitors for the novel SARS Cov-2 virus and have more future in discovery of potent drug candidates. [ABSTRACT FROM AUTHOR]

A novel series of benzofuran bearing thiazole hybrids were synthesized by the multistep reaction approach. All synthesized molecules were selected by the National Cancer Institute, USA for one-dose anticancer activity against 60 various human cancer cell lines indicating nine types of cancer. Among thirteen compounds, two compounds showed higher lethality, so, it was selected for five-dose anticancer screening against all cancer cell lines. Compound 8g and 8h were displayed remarkable antiproliferative activity with GI50 values ranging from 0.295 to 4.15 μM and LC50 values ranging from 4.43 to > 100 μM. All data are compared with standard drugs fluorouracil and doxorubicin. Compound 8g showed higher potency as a cytotoxic molecule then fluorouracil. Furthermore, all new hybrids were studied for molecular docking into the active binding sites of 1HOV protein. [ABSTRACT FROM AUTHOR]

The reaction of 4-chlorobenzohydrazide 1 with carbon disulphide in the presence of methanolic potassium hydroxide afforded 4-chloro potassium dithiocarbohydrazide 2. The intermediate 2 reacts with a solution of hydrazine hydrate in water gave 4-amino-5(4-chlorophenyl)-4H-[1,2,4]-triazole-3-thiol 3. Condensation of 3 with various substituted phenacyl bromide in alcohol afforded series of 1,2,4-triazolo-[3,4-b][1,3,4]thiadiazine analogs 4a–4l bearing 4-chlorophenyl moiety. The structures of newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR and mass spectroscopy techniques. All synthesized compounds 4a–4l were screened for anti-inflammatory activity by carrageenan induced paw edema using albino Wistar rats. In addition, molecular docking study was performed for 4a—4l using prostaglandin D2 synthase (PGDS) enzyme receptor binding pocket. Compounds 4l and 4b exhibited significant anti-inflammatory activity (P < 0.01), whereas compounds 4b, 4f, and 4k unveiled good anti-inflammatory activity (P < 0.05) when compared with standard drug indomethacin. [ABSTRACT FROM AUTHOR]

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been the most commonly used class of medications worldwide for the last three decades. Objectives: This study aimed to design and synthesize a novel series of methoxyphenyl thiazole carboxamide derivatives and evaluate their cyclooxygenase (COX) suppressant and cytotoxic properties. Methods: The synthesized compounds were characterized using 1H, 13C-NMR, IR, and HRMS spectrum analysis and were evaluated for their selectivity towards COX-1 and COX-2 using an in vitro COX inhibition assay kit. Besides, their cytotoxicity was evaluated using the Sulforhodamine B (SRB) assay. Moreover, molecular docking studies were conducted to identify the possible binding patterns of these compounds within both COX-1 and COX-2 isozymes, utilizing human X-ray crystal structures. The density functional theory (DFT) analysis was used to evaluate compound chemical reactivity, which was determined by calculating the frontier orbital energy of both HOMO and LUMO orbitals, as well as the HOMO–LUMO energy gap. Finally, the QiKProp module was used for ADME-T analysis. Results: The results revealed that all synthesized molecules have potent inhibitory activities against COX enzymes. The percentage of inhibitory activities at 5 µM concentration against the COX2 enzyme was in the range of 53.9–81.5%, while the percentage against the COX-1 enzyme was 14.7–74.8%. That means almost all of our compounds have selective inhibition activities against the COX-2 enzyme, and the most selective compound was 2f, with selectivity ratio (SR) value of 3.67 at 5 µM concentration, which has a bulky group of trimethoxy on the phenyl ring that could not bind well with the COX-1 enzyme. Compound 2h was the most potent, with an inhibitory activity percentage at 5 µM concentration of 81.5 and 58.2% against COX-2 and COX-1, respectively. The cytotoxicity of these compounds was evaluated against three cancer cell lines: Huh7, MCF-7, and HCT116, and negligible or very weak activities were observed for all of these compounds except compound 2f, which showed moderate activities with IC50 values of 17.47 and 14.57 µM against Huh7 and HCT116 cancer cell lines, respectively. Analysis of the molecular docking suggests 2d, 2e, 2f, and 2i molecules were bound to COX-2 isozyme favorably over COX-1 enzyme, and their interaction behaviors within COX-1 and COX-2 isozymes were comparable to celecoxib, as an ideal selective COX-2 drug, which explained their high potency and COX-2 selectivity. The molecular docking scores and expected affinity using the MM-GBSA approach were consistent with the recorded biological activity. The calculated global reactivity descriptors, such as HOMO and LUMO energies and the HOMO–LUMO gaps, confirmed the key structural features required to achieve favorable binding interactions and thus improve affinity. The in silico ADME-T studies asserted the druggability of molecules and have the potential to become lead molecules in the drug discovery process. Conclusion: In general, the series of the synthesized compounds had a strong effect on both enzymes (COX-1 and COX-2) and the trimethoxy compound 2f was more selective than the other compounds. [ABSTRACT FROM AUTHOR]

Recently, indoles are considered interesting heterocyclic compounds due to their wide range of biological activities such as antimicrobial activity. Herein, some new indole derivatives containing heterocyclic moieties were synthesized using 1H-indol-5-ylamine as a starting material, then allowed to convert to diazonium salt (1) which used for synthesis of new azo dyes (2, 3 and 4) by coupling with salicylaldehyde, o-cresol and phenol. The reaction of diazonium salt (1) with acetyl acetone afforded hydrazine (5) which was reacting with active methylene compounds (malononitrile, ethyl cyanoacetate) to give pyridazine derivatives (8, 9). The reaction of parent compound with thioisocyanate was produced Compound (10) which cyclized with phenacyl bromide to form thiazole derivative (11). Treatment of parent compound with hydrazine was gave compound (12) which consider as a key for many Schiff bases (13, 14, 15 and 16) and its derivatives such as oxazepine, thiazolidinone, β-lactam and pyrazol derivatives (17, 18, 19 and 20), respectively.Compound (14) under went to react with active methylene compounds (malononitrile, ethyl acetoacetate) to afford derivatives (21, 22) while when (14) was treated with hydroxyl amine in presence of sodium acetate gave (23). The latter was produced derivatives (24, 25) when treated with benzoyl chloride, benzyl chloride, respectively, while was afforded (26) when allowed to react with acetic anhydride. At last treatment of (26) with hydrazine formed derivative (27). The structures, of all synthesized compounds were confirmed using spectroscopic analysis such as UV, FTIR, 1HNMR and 13C–NMR. [ABSTRACT FROM AUTHOR]

In this study, a new tandem method was developed for the synthesis of thiazole-substituted pyrrolo[1,2-d][1,2,4]triazin-4(3H)-one derivatives. The method consists of a tandem reaction involving a subsequent formation of first the thiazole and then the triazine ring upon the addition of phenacyl bromide to a product of the condensation reaction between ethyl 2-formyl-1H-pyrrole- 1-carboxylate and thiosemicarbazide. The tandem cyclization step was completed in just 30 minutes. In order to predict the reaction mechanism, the charge densities of atoms and HOMO and LUMO energy were calculated by DFT method for the compounds obtained in the intermediate stage. In addition, a series of pyrrolotriazinone derivatives synthesized in high yields by this method were found to be suitable drug candidates according to their druglikeness and theoretical pharmacokinetic profiles. [ABSTRACT FROM AUTHOR]

A series of N-(thiazol-4-ylmethyl) benzenesulfonamide derivatives were designed, synthesized, and characterized by 1H NMR, 13C NMR, and HRMS. The evaluation of fungicidal activities against Fusarium oxysporum (F. oxysporum), Sclerotinia sclerotiorum (S. sclerotiorum), Botrytis cinerea (B. cinerea), Colletotrichum fragariae (C. fragariae), Alternaria alternata (A. alternata), Penicillium digitatum (P. digitatum), Curvularia lunata (C. lunata), and Curvularia mebaldsii (C. mebaldsii) for the target compounds was carried out. The results indicated that this series of compounds were sensitive to C. lunata, B. cinerea, and S. sclerotiorum. Especially, 2,4-dichloro-N-((2-phenylthiazol-4-yl)methyl)benzenesulfonamide (5c) exhibited the best bioactivities against C. lunata, B. cinerea, and S. sclerotiorum with EC50 value of 20.8 mg/L (52.3 μM), 24.6 mg/L (61.8 μM), and 9.5 mg/L (23.9 μM), respectively, which has equivalent or superior fungicidal activity to commercial products hymexazol. Furthermore, the structure–activity relationship was given, which might be contribution to the design and discovery of N-(thiazol-4-ylmethyl)benzenesulfonamide derivatives as novel fungicide. [ABSTRACT FROM AUTHOR]

A series of flavonoid derivatives containing thiazole scaffold were designed, synthesized and evaluated for their inhibition effects against Rhizoctonia solani, Fusarium graminearum, Gaeumannomyces graminis, Alternaria solani, Botrytis cinerea, and Alternaria mali. The antifungal bioassays results in vitro indicated that some target compounds showed good antibacterial activity against the tested plant fungi, which were better than that of the flavonoid natural product quercetin. Strikingly, the title compounds 6a, 6b, and 6f demonstrated obvious antifungal activities against Rhizoctonia solani with EC50 value of 9.6, 35.5, and 21.5 μg/mL, respectively. The EC50 value of compound 6b against Gaeumannomyces graminis reached 2.7 μg/mL. [ABSTRACT FROM AUTHOR]

The selectivity of alkylation of malononitrile derivatives with α-bromocarbonyl compounds has been studied. The structure of some alkylation products has been studied by X-ray analysis. [ABSTRACT FROM AUTHOR]

The goal of this research work was to prepare and evaluate the antitubercular (anti-TB) activity of ethionamide (ETH) and prothionamide (PTH) based coumarinyl-thiazole derivatives. ETH and PTH were reacted with coumarin intermediates (3a-3e) to provide the target compounds (4a-4e and 4f-4j, respectively). Spectral studies confirmed the assigned structures of 4a-4j. The Microplate Alamar Blue Assay was utilized to evaluate the anti-TB activity of compounds 4a-4j against Mycobacterium tuberculosis H37Rv strain in comparison to ETH, PTH, isoniazid (INH), and pyrazinamide (PYZ) as standard drugs. The cytotoxicity studies were carried out versus HepG2 and Vero cell lines. In addition. molecular docking studies of 4a-4j concerning the DprE1 enzyme and the in-silico evaluation of physicochemical and pharmacokinetic parameters were performed. Compounds 4a, 4b, 4f, and 4g displayed equal minimum inhibitory concentration (MIC) values in comparison to INH (3.125 μg/ml) and PYZ (3.125 μg/ml), whereas 4c-4e and 4h-4j displayed better MIC values (1.562 μg/mL) than INH and PYZ. All compounds presented better anti-TB potential than ETH (6.25 μg/mL) and PTH (6.25 μg/mL). The studies of toxicity revealed that 4a-4j were safe up to 300 μg/mL concentration versus Vero and HepG2 cell lines. The molecular docking studies suggested that 4a-4j could possess anti-TB activity through the inhibition of the DprE1 enzyme. The in silico studies showed that 4a-4j followed Lipinski's rule (drug-likeliness) and exhibited better gastrointestinal absorption than BTZ043 and macozinone. In conclusion, the ETH and PTH-based coumarinyl-thiazole template can help developing selective DprE1 enzyme inhibitors as potent anti-TB agents. [ABSTRACT FROM AUTHOR]

In present pandemic situations, we need more and more care on the medication, to treat the ill cells or to control the growth of the cells we need better transfection with active pharmaceutical ingredients. In chemotherapy many drugs are working on the target as well as on adjacent organs, to avoid such conditions, we required active compounds, coumarin, and thiazole-based compounds can function in this way. This research work illustrated better transfection and percentage of cell viability of azetidinones by the insertion of thiazole and (or) coumarin groups. Synthesized the tilted compounds from Thiazole (or) Coumarin-based Schiff base, and chloroacetyl chloride with good yields. Herein, the β-lactam group acts as a linker, to this linker one side heterocyclic ring acts as the anchoring group, and the other side of the aromatic ring acts as the hydrophobic group; in silico studies of this series, results have shown that many compounds are having anti-cancer activity along with other biological activities. The in vitro cell viability studies IC50 values of Azetidinone (III): 1.5608, (IV): 1.5694, (V): 1.5489, and (VI): 1.7452 are better than the reference Lipofectamine 2000 (L2K): 2.0280 against oral cancer cell line (CAL-27), this result supported by the cellular uptake against HEK-293, DNA binding, and β-galactose activity. [ABSTRACT FROM AUTHOR]

A series of new thiazole based hydrazones have been synthesized and their antimicrobial and α-amylase (type-II diabetes) inhibitory activities have been evaluated. The structures of synthesized derivatives were elucidated by various spectral techniques including FTIR, NMR and mass spectrometry. Antibacterial activity tests were performed against two Gram-positive (Bacillus subtilis and Staphylococcus aureus) and two Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacterial strains. Two fungal strains (Candida albicans and Aspergillus niger) were taken for testing antifungal activity. Among the tested derivatives, compound 3d was found to be the most potent against all tetsed bacterial and fungal strains. The α-amylase inhibitory activity of all compounds was also assayed using the starch iodine method. Derivatives 3j and 3k exhibited the best inhibitory activity against α-amylase enzyme with IC50 values of 0.26 ± 0.06 and 0.32 ± 0.02 μM, respectively, in comparison to acarbose (IC50 = 0.11 ± 0.00 μM) as standard reference. The results of the biological activity evaluation were confirmed by docking studies. [ABSTRACT FROM AUTHOR]

Some urea-thiazole/benzothiazole hybrids with a triazole linker were synthesized via Cu(I)-catalysed click reaction. After successfully analysed by various spectral techniques including FTIR, NMR and HRMS, antimicrobial screening of the synthesized hybrids along with their precursors was carried out against two Gram (+) bacteria (Staphylococcus aureus and Bacillus endophyticus), two Gram (−) bacteria (Escherichia coli and Pseudomonas fluorescens) and two fungi (Candida albicans and Rhizopus oryzae). All the synthesized compounds (4a–4l) displayed better biological response than the standard fluconazole against both of the tested fungi. Compounds 4h and 4j were found to be the most active compounds against R. oryzae and C. albicans, respectively. Molecular docking of hybrid 4j and its alkyne precursor 1b in the active site of C. albicans target sterol 14-α demethylase was also performed and was also supported by molecular dynamics studies. In silico ADME prediction of synthesized urea-thiazole/benzothiazole hybrids with a triazole linker and their alkyne precursors was also predicted. [ABSTRACT FROM AUTHOR]

Twelve new heterocyclic Schiff bases were synthesized by condensation of 2-acetylthiazole and 2-butyl-4-chloro-1H-imidazole-4-carbaldehyde with substituted anilines by the simple and low-cost SnCl4-mediated grinding method. Among the synthesized compounds, three derivatives showed a good herbicidal activity, and two compounds showed excellent activity. [ABSTRACT FROM AUTHOR]

Condensation reactions of diphenylphosphine, 2-(benzo[d]thiazol-2-yl)aniline (NH2-pbt) and a series of aldehydes RC(O)H (R = phenyl, 2-furanyl and 4-pyridyl) are carried out to obtain α-aminophosphines Ph2P(O)C(R)NH-pbt. In the case of phenyl and 2-furanyl derivatives, respective compounds 1 and 2 are isolated with a yield of 80-85%, and 4-pyridyl analogue 3 is obtained in an insignificant amount. According to single crystal X-ray diffraction data, the compounds crystallize in the chiral space group P212121, forming crystals containing only R- or S-enantiomers. Additional substituents R do not strongly affect the spatial geometry of molecules. The photophysical properties of compounds 1 and 2 are similar, and this means that the additional substituents contribute equally to the character of electronic transitions in the compounds. [ABSTRACT FROM AUTHOR]

A reaction of 2-(4,4,6-trimethyl-2-oxo-4H-pyrrolo[3,2,1-ij]quinoline-1-ylidene)-hydrazinocarbothioamides with α-halocarbonyl compounds, such as ethyl bromocetate and 2-bromoacetophenone derivatives, afforded a series of novel 4,4,6-trimethyl-2-oxo-4H-pyrrolo[3,2,1-ij]quinoline-1(2H)-ylidene)hydrazinylidene)thiazolidin-4-ones and 4,4,6-trimethyl-1-(2-(4-arylthiazol-2-yl)hydrazinylidene)-4H-pyrrolo[3,2,1-ij]quinolin-2(1H)-ones. The synthesized compounds exist in the form of Z-isomers. Primary screening in vitro of inhibitory activity towards blood clotting factors Xa and XIa was carried out, revealing that the thiazole derivative bearing the 4-chlorophenyl substituent at the thiazole moiety exhibits a sufficiently high anticoagulant activity towards these blood clotting factors. [ABSTRACT FROM AUTHOR]

A simple and efficient method of synthesis of 1-[5-(4-methylthiazol-5-yl)-2-phenyl-1,3,4-oxadiazol-3(2H)-yl]ethanone from (E)-N′-benzylidene-4-methylthiazole-5-carbohydrazides and acetic anhydride has been developed. Structures of the synthesized compounds have been confirmed by IR, 1H and 13C NMR, and mass spectra. All compounds have been tested for their in vitro antibacterial and antifungal activity. Molecular docking study has been carried out for deeper insight in the antimicrobial action and prediction of the binding modes of these compounds. In silico ADMET predictions and pharmacokinetic studies confirm high oral bioavailability of the products. The results of in vitro and in silico studies suggest that thiazole and oxadiazole incorporated heterocycles can match the structural requirements for further development of novel therapeutic agents. [ABSTRACT FROM AUTHOR]

The selective olefination of a variety of aromatic aldehydes with the use of ethyl diazoacetate catalyzed by heterogeneous copper(II) complex of 3,5-bis(2–benzothiazolyl)pyridine, [Cu(II)(BTP)(OTf)2], immobilized on silica nanoparticles and chloromethylated polystyrene, [Cu(II)(BTP)(OTf)2]@TMSP-nSiO2, [Cu(II)(BTP)(OTf)2]@CMP, in the presence of triphenylphosphine. These reactions were done in excellent yields (> 85%), with remarkable selectivity for the E-isomer, time of reaction is short, and condition of reaction is mild. The mechanism of olefination was investigated, and the possible pathway is discussed. In this manner, the catalytic activity of the heterogeneous catalyst was investigated, and results showed that we could use this catalyst numerous times, and catalytic activity did not decrease. [ABSTRACT FROM AUTHOR]

In this study, a thiazolopyrimidine derivative ethyl 2-(2-acetoxyphenyl)-5-(4 (benzyloxy) phenyl)-7-methyl-3-oxo-3,5-dihydro-2H-thiazolo[3,2-a]pyrimidine-6 carboxylate (EAPC) was investigated experimentally and theoretically. FMOs (frontier molecular orbitals), MEP, ALIE surfaces and solvation free energies were calculated for EAPC at CAM-B3LYP/6–311++G(2d,p) level. Solvation free energies in water, ethanol, acetone, acetonitrile, and chloroform were obtained and the analysis of the energy values suggests that acetone and acetronitrile may be better for solubilization of EAPC. However, the value of solvation energy in water (hydration free energy) indicates good solubility of the studied molecule in an aqueous medium, factor that corroborates the biological activity. Vibrational analysis, together with potential energy distribution (PED) calculations, revealed several characteristic vibrations. Molecular docking and molecular dynamics simulations carreid out with angiotensin I-converting enzyme revealed that EAPC is a promising antihypertensive candidate. [ABSTRACT FROM AUTHOR]

In the present study, a new series of 3-(2,5-dichlorothiophen-3-yl)-5-aryl-4,5-dihydro-1H-pyrazole-1-carbothioamides 2 were synthesized either by the reaction of (E)-3-aryl-1-(2,5-dichlorothiophen-3-yl)prop-2-en-1-ones 1 with thiosemicarbazide or by one-pot reaction of 3-acetyl-2,5-dichlorothiophene with the corresponding aldehyde and thiosemicarbazide. Additionally, 2-(3-(2,5-dichlorothiophen-3-yl)-5-aryl-4,5-dihydro-1H-pyrazol-1-yl)-4-phenylthiazoles 3 were synthesized in 46–89% yields by the reflux of carbothioamides 2 with 2-bromoacetophenone. The structures of the newly synthesized compounds were characterized by IR, 1H-NMR, 13C-NMR, DEPT-135, and mass spectrometry analysis (MS). All new compounds were evaluated as antimicrobial and antioxidants. Compound (3b) exhibited moderate activity against Bacillus subtilis and Penicillium fimorum, 14 ± 0.5 mm and 18 ± 0.75 mm, respectively, while the other synthesized compounds did not show activity against the tested microbes. The most potent antioxidant activity showed by compound (2a) and (2e) with 95.2% and 96.3%, which considered good to excellent antioxidant activity compared with the control (ascorbic acid) and other synthesized compounds. Molecular docking study of the new compounds with cytochrome P450 14 alpha-sterol demethylase (CYP51) was carried out to evaluate their possibility as drugs and to implement structural improvements for this purpose. All synthesized compounds exhibited good affinity with (CYP51), notably, (3a) and (3b) compounds showed the highest affinity with the lowest binding energies. [ABSTRACT FROM AUTHOR]

Some novel pyrazoline derivatives bearing thiazole and thiophene moieties have been efficiently synthesized and characterized. The synthetic approach involves condensation of 5-acetylthiazole 1 with 2-formyl thiophene 2 followed by heterocyclization of the produced chalcone 3 with hydrazine and thiosemicarbazide under different conditions to give selectively 1-substituted-3-(thiazol-5-yl)-5-(thiophen-2-yl)pyrazolines 4–6 and 8 in high yields. Heterocyclization of 1-thicarbomylpyrazoline 8 with 3-chloro-2,4-pentanedione, phenacyl bromide and hydrazonoyl bromides in boiling ethanol and TEA results in the respective 1-(thiazol-2-yl)-3-(thiazol-5-yl)-5-(thiophen-2-yl)pyrazolines 11, 12, and 14a–14f. Anticancer activity of the novel 1,3,5-trisubstituted pyrazolines has been evaluated, against breast (MCF-7), liver (HepG2), and colon (HCT-116) cancer cell lines, as well as epithelial (REP1) normal cell line. Among the synthesized pyrazolines, compounds 8, 14a, and 14f demonstrate the highest anticancer activity with IC50 values of 1.83, 5.47, and 11.43 µM, respectively, and presenting no evidence of human toxicity. [ABSTRACT FROM AUTHOR]

A series of new benzamidine derivatives have been synthesized in good yields by involving 1-(1H-benzimidazol-2-yl)-2-bromoethanone, 4-(1H-benzimidazol-2-yl)-1,3-thiazol-2-amine, and N-benzyli-dene-4-(1H-benzimidazol-2-yl)-1,3-thiazol-2-amine as reactive intermediates. The synthesized compounds were characterized by spectral data. Molecular docking study of N-(4-(1H-benzimidazol-2-yl)-1,3-thiazol-2-yl]-1-[(E)-phenyldiazenyl]-1-phenylmethanimine has been carried out as a representative case. [ABSTRACT FROM AUTHOR]

A clean and efficient, multi-component strategy for the synthesis of biologically important trisubstituted thiazole via the reaction of readily available barbituric acid, acetophenone, and aryl thioamides is reported in the presence of FeCl3.6H2O / O2(Air) in DMF solvent. The advantages of the present methodology include a one-pot reaction, environment-friendly approach, cost-effectiveness, broad substrate scope, operational simplicity, short reaction time, easy workup procedure, and high yields. [ABSTRACT FROM AUTHOR]

The ethyl 2-[2-(2-nitrobenzylidene)hydrazinyl]thiazole-4-carboxylate (1), a thiazole ester, was synthesized by refluxing 1-(2-nitrobenzylidene)thiosemicarbazide and ethyl bromopyruvate. The compound is characterized by spectrometric, spectroscopic and single crystal (SC-XRD) techniques. Non-covalent interactions that are responsible for crystal packing are explored by Hirshfeld surface analysis. All theoretical calculations were performed by DFT quantum chemical methods using 6-311G(d,p) and cc-pVTZ basis sets and compared. Theoretical harmonic frequencies of ethyl 2-[2-(2-nitrobenzylidene)hydrazinyl]thiazole-4-carboxylate (1) were optimized. Confirmation of hydrogen bonding sites was analyzed by molecular electrostatic potential (MEP) and Mulliken population analysis. The vibrational frequencies of characteristic functional groups and chemical shifts were found in good agreement with experimental assignments. Frontier molecular orbital (FMO) revealed relatively small HOMO–LUMO (highest occupied molecular orbital-lowest unoccupied molecular orbital) gape, which speaks off the nearly planar geometry and extended conjugation, as compared to the substituents with no conjugation possible. It has also been observed that –NO2 substituent plays a vital role for this relatively small HOMO–LUMO gape and overall electronic properties when compared with similar thiazole carboxylates (2–6, Table 6). Ethyl 2-[2-(2-nitrobenzylidene)hydrazinyl]thiazole-4-carboxylate (1) was also evaluated for its anti-oxidant and anti-microbial activities. [ABSTRACT FROM AUTHOR]

We report the synthesis of non-peripheral metallophthalocyanines which carry four 4-(4-methoxyphenyl)-2-thiazole-2-thio units. 1H-NMR, FT-IR, UV–Vis, and MS data were acquired to characterize the synthesized compounds. Voltammetric and in situ spectroelectrochemical measurements shed light on the redox properties of the metallophthalocyanines (MPcs) in order to show the influence of the metal cations and thiazole-bearing substituents. In solution, the redox processes had an influence to the electrochromic responses, which were examined with in situ spectrocolorimetry. Phthalocyanines having cobalt (II), manganese (III), iron (III), and zinc (II) at the center yielded characteristic redox couples which are metal- and/or Pc-based and which are harmonious with the common redox properties of these types of compounds. In situ spectroelectrochemistry provided the information that MPc species underwent distinct color changes during electron transfer reactions. Electropolymerization of all complexes was performed on glassy carbon electrode, and the electropolymerized film of FePc was evaluated as an active electrocatalyst, in the alkaline medium, for oxygen evolution reaction (OER). [ABSTRACT FROM AUTHOR]

Benzobisthiazole polymer with resonance-assisted hydrogen bonds (RAHBs) has been synthesized for both organic field-effect transistor and polymer solar cell applications. The properties of the hydrogen bonded polymer are compared with the reference polymer without RAHBs. Single-crystal X-ray diffraction analyses of the building block reveal that the RAHB interactions are formed between the carbamate hydrogen and imine nitrogen of the thiazoles. The hydrogen donor and acceptor are connected by π-conjugated molecular framework and the hydrogen-bridged quasi aromatic rings lock the conformation of the building block. The building block adopted a layered sandwich packing in crystal instead of slipped herringbone stacking which was often found in the crystal of benzobisthiazole derivatives. The polymer PCBTZ-TT with RAHBs showed deeper HOMO/LUMO energy level (about 0.2 eV) than reference polymer. The PCBTZ-TT demonstrated the hole mobility of 0.96 cm2·V−1·s−1 in field-effect transistor devices and achieved power conversion efficiency of 13.6% in solar cell devices with Y6 as acceptor without any additive. [ABSTRACT FROM AUTHOR]

N-Arylthioureas were reacted with hydrogen peroxide to synthesize 5-imino-N,4-diaryl-4,5-dihydro-1,2,4-thiadiazol-3-amines (Ar = Ph, p-Tol, 4-BrC6H4). The products undewent 1,3-dipolar cycloaddition to (R-ethynyl)sulfonyl benzoles (R = Me, Ph, p-Tol, CF3) under mild conditions to form, in each case, a mixture of the corresponding 5-sulfonyl-substituted N,4-diarylthiazole-2-amines and N-arylcyanamides. [ABSTRACT FROM AUTHOR]

The condensation of maleopimaric acid or its chloride with 2-aminothiazole or 2-aminobenzothiazole afforded new maleopimaric acid imides and amides containing thiazole or benzothiazole fragments. Maleo-pimaric acid chloride reacted with 2-aminothiazole at room in anhydrous methylene chloride at room tempera-ture to give a mixture of the corresponding N-thiazolyl amide and a maleopimaric acid derivative containing a thiazole ring in both carboxylic acid and anhydride moieties at a ratio of 7:2. [ABSTRACT FROM AUTHOR]

Background: Thiazole-based Schiff base compounds display significant pharmacological potential with an ability to modulate the activity of many enzymes involved in metabolism. They also demonstrated to have antibacterial, antifungal, anti-inflammatory, antioxidant, and antiproliferative activities. In this work, conventional and green approaches using ZnO nanoparticles as catalyst were used to synthesize thiazole-based Schiff base compounds. Results: Among the synthesized compounds, 11 showed good activities towards Gram-negative E. coli (14.40 ± 0.04), and Gram-positive S. aureus (15.00 ± 0.01 mm), respectively, at 200 μg/mL compared to amoxicillin (18.00 ± 0.01 mm and 17.00 ± 0.04). Compounds 7 and 9 displayed better DPPH radical scavenging potency with IC50 values of 3.6 and 3.65 μg/mL, respectively, compared to ascorbic acid (3.91 μg/mL). The binding affinity of the synthesized compounds against DNA gyrase B is within − 7.5 to − 6.0 kcal/mol, compared to amoxicillin (− 6.1 kcal/mol). The highest binding affinity was achieved for compounds 9 and 11 (− 6.9, and − 7.5 kcal/mol, respectively). Compounds 7 and 9 displayed the binding affinity values of − 5.3 to − 5.2 kcal/mol, respectively, against human peroxiredoxin 5. These values are higher than that of ascorbic acid (− 4.9 kcal/mol), in good agreement with the experimental findings. In silico cytotoxicity predictions showed that the synthesized compounds Lethal Dose (LD50) value are class three (50 ≤ LD50 ≤ 300), indicating that the compounds could be categorized under toxic class. Density functional theory calculations showed that the synthesized compounds have small band gap energies ranging from 1.795 to 2.242 eV, demonstrating that the compounds have good reactivities. Conclusions: The synthesized compounds showed moderate to high antibacterial and antioxidant activities. The in vitro antibacterial activity and molecular docking analysis showed that compound 11 is a promising antibacterial therapeutics agent against E. coli, whereas compounds 7 and 9 were found to be promising antioxidant agents. Moreover, the green synthesis approach using ZnO nanoparticles as catalyst was found to be a very efficient method to synthesize biologically active compounds compared to the conventional method. [ABSTRACT FROM AUTHOR]

A series of sixteen oxadiazole derivatives containing a thiazole ring were synthesized, characterized by different spectroscopic techniques (1H and 13C NMR, EI HRMS) and evaluated for their in vitro thymidine phosphorylase inhibitory activity. All compounds showed good to excellent thymidine phosphorylase inhibitory activity with IC50 values ranging between 32.40±0.01 to 54.10±0.02 µM, and three of them proved to be more active than the standard drug 7-deazaxanthine (IC50 = 38.68±1.12 µM). Molecular docking study was carried out on the most active compounds in order to identify their interactions with the active site of the enzyme. Structure–activity relationship was also analyzed on the basis of substitution pattern on the phenyl ring. [ABSTRACT FROM AUTHOR]

A bimannich-based TZBM containing a thiazole ring was obtained by synthesis of mannich bases. TZBM featured a stable structure at 260 °C, and corrosion inhibition effect on carbon steel in a gas–liquid environment with Cl− + H2S + CO2 at 180 °C. By analyzing the weight loss of steel exposed to different TZBM concentrations, the coverages of the inhibitor adsorbed on the surfaces were determined, and the results conformed to Langmuir isotherm model. Furthermore, the negative Gibbs free energy indicated that the adsorption was a spontaneous process. [ABSTRACT FROM AUTHOR]

Isolated polynuclear binary heterocyclic compounds containing thiazole building block combined with benzofuran, pyrrole, thiazole, or thiophene via carboxamide and/or secondary amine as a junction are presented. The synthetic strategy of those is based on utilization of 2-chloroacetamido-4-phenylthiazole in the synthesis of binary heterocyclic compounds by cyclocondensation with salicylic aldehyde, acetonitrile derivatives, ammonium thiocyanate, 3-mercaptoacrylonitrile derivatives, and/or 3-mercaptoacrylate derivatives. The prepared binary thiazole-based heterocycles have been studied as protease (Mpro) inhibitors by molecular docking for visualization of their orientation and interactions with COVID-19 units using hydroxychloroquine as a reference molecule. [ABSTRACT FROM AUTHOR]

The present minireview concerns the application of cyclic isothiourea moiety (with endocyclic sulfur atom) in drug design and includes the examples of bioisosteric replacement, conformational restriction, etc. The synthetic procedures leading to the target structures of cyclic isothioureas and their bicyclic derivatives are also discussed. The review gives multiple useful examples for the chemists searching novel heterocyclic compounds with neuroprotective, antihypotensive, antiproliferative, antiobestic, and analgetic properties. [ABSTRACT FROM AUTHOR]

Recently, the occurrence of candidiasis has increased dramatically, especially in immunocompromised patients. Additionally, their treatment is often ineffective due to the resistance of yeasts to antimycotics. Therefore, there is a need to search for new antifungals. A series of nine newly synthesized thiazole derivatives containing the cyclopropane system, showing promising activity against Candida spp., has been further investigated. We decided to verify their antifungal activity towards clinical Candida albicans isolated from the oral cavity of patients with hematological malignancies and investigate the mode of action on fungal cell, the effect of combination with the selected antimycotics, toxicity to erythrocytes, and lipophilicity. These studies were performed by the broth microdilution method, test with sorbitol and ergosterol, checkerboard technique, erythrocyte lysis assay, and reversed phase thin-layer chromatography, respectively. All derivatives showed very strong activity (similar and even higher than nystatin) against all C. albicans isolates with minimal inhibitory concentration (MIC) = 0.008–7.81 µg/mL Their mechanism of action may be related to action within the fungal cell wall structure and/or within the cell membrane. The interactions between the derivatives and the selected antimycotics (nystatin, chlorhexidine, and thymol) showed additive effect only in the case of combination some of them and thymol. The erythrocyte lysis assay confirmed the low cytotoxicity of these compounds as compared to nystatin. The high lipophilicity of the derivatives was related with their high antifungal activity. The present studies confirm that the studied thiazole derivatives containing the cyclopropane system appear to be a very promising group of compounds in treatment of infections caused by C. albicans. However, this requires further studies in vivo. Key points: • The newly thiazoles showed high antifungal activity and some of them — additive effect in combination with thymol. • Their mode of action may be related with the influence on the structure of the fungal cell wall and/or the cell membrane. • The low cytotoxicity against erythrocytes and high lipophilicity of these derivatives are their additional good properties. [ABSTRACT FROM AUTHOR]