Synthesis and antimicrobial, antiproliferative evaluation of novel quinolone and conazole analogues via conventional and microwave techniques

1,2,4-Triazole-3-one (3), acquired from cinnamaldehyde was converted to the corresponding carbox(thio)amides via several steps (6 a–c). Their reaction with sodium hydroxide gave the 1,2,4-triazole derivatives (7 a–c). Compound 3 treatment with 2-bromo-1-(4-chlorophenyl) ethanone or 2-chloro-1-(2,4-dichlorophenyl)ethanone afforded the compounds 8 a,b and by reducing these compounds reduction products were obtained (9 a,b). The synthesis of (10 a–e) was carried out by the reaction compounds 9 a,b with different benzyl chlorides. Then oxadiazole derivative (12) was obtained by ring closure from hydrazide compound 5. Subsequently compounds 3, 7 a–c, and 12 were treated with various amines in the presence of formaldehyde to yield Mannich bases (11 a–e, 14 a–e, 13 a,b). Microwave-assisted and conventional techniques were utilized for the syntheses. The structures of newly synthesized compounds were illuminated by spectroscopic methods. Their antimicrobial (MIC method), and anticancer activities (Abay's method) were examined. Results showed that most of the compounds exhibited good antimicrobial activities. Especially compounds 14 a–e which is a mannich base showed very good antitubercular activity against Mycobacterium smegmatis compared with Streptomycin standard drug. Also compounds 8 a and 9 b have been found to have strong antiproliferative effects on the HeLa cervical cancer cells and also these compounds did not have a cytotoxic effects on a normal cells

Antimicrobial, antioxidant and antiproliferative activities of novel quinolones

The compound (2) formed by esterification of dimethyl morpholine (1) was converted to acetohydrazide (3). Subsequently Schiff bases (4 a-d) and carboxy(thio)amide derivatives (5 a-e) were synthesized. Then 1,2,4-triazole (6 a-e), thia(oxa)zolidine (7 c,e) and thia(oxa)zol (8 c,e) derivatives were obtained by ring closure from carboxy(thio)amides. Mannich bases, which are containing quinolone were synthesized from 1,2,4-triazoles. The structures of newly synthesized compounds were illuminated by spectroscopic methods. Their antimicrobial (MIC method), antioxidant (DPPH, FRAP, and CUPRAC methods), and anticancer activities (MTT method) were examined. Results showed that most of the compounds exhibited good antimicrobial (<0.03-31.25 mu g/mL with MIC values) and antioxidant activities (IC50=0.001-0.004 with DPPH values). Also, some of the compounds have been found to have antiproliferative effects on the prostate (PC-3), liver (Hep3B), and breast (MCF-7) human cancer cells, and also these compounds did not have a cytotoxic effect on a normal cell.This work was supported by Artvin Coruh University, BAP (2016.F11.02.06), Turkey

Microwave-assisted synthesis of some hybrid molecules derived from morpholine and investigation of their antimicrobial activities

2H-1,2,4-triazol-3(4H)-one compound was obtained starting from 4-(2-fluoro-4-nitrophenyl)morpholine via several steps. Then, these compounds were converted to the corresponding fluoroquinolone hybrids via one pot three component Mannich reaction. Moreover, the synthesis of eleven compounds, which can be considered as conazole analogues, was performed starting from 1,2,4-triazole-3-one compounds via three steps by either conventional or microwave mediated conditions. The effect of different solvents and microwave power on microwave prompted reactions was examined as well

Quinolone-rhodanine hybrid compounds: Synthesis and biological evaluation as anti-bacterial agents

As potential antimicrobial agents, 4-fluoroaniline and diethyl (ethoxymethylene)malonate were used to efficiently synthesize a new quinolone (3-9) series. The (HNMR)-H-1 and C-13 NMR, IR, mass spectrometry, and elemental analysis of all compounds were used to identify them. The final compounds 3-9 were in vitro screened for antimicrobial activity against gram negative-gram positive Escherichia coli, Yersinia pseudotuberculosis, Pseudomonas aeruginosa, Staphylococcus aureus, Enterococcus faecalis, Bacillus cereus, Mycobacterium smegmatis and fungal strains Candida albicans, Saccharomyces cerevisiae. The best antimicrobial activity was demonstrated by compounds 9a and 9b. Antimicrobial resistance and microbial infection could benefit from quinolone derivatives ' ability to inhibit the growth of microorganisms, according to this study

Design and microwave-assisted synthesis of a novel Mannich base and conazole derivatives and their biological assessment

4-Amino-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (1) was converted to the corresponding Schiff base (2) by treatment with salicylaldehyde. 1,2,4-Triazoles were then converted to the corresponding Mannich bases containing fluroquinolone core using a one-pot three-component procedure. Moreover, the synthesis of six compounds, which can be considered as conazole analogues, was performed starting from 1,2,4-triazole-3-one compounds via three steps by either conventional or microwave-mediated conditions. All the newly synthesized compounds were screened for their antimicrobial activities. Most exhibited good to moderate antibacterial and/or antifungal activity. The structural assignments of the new compounds were based on elemental analysis and spectral (IR, H-1 NMR, C-13 NMR, and LC-MS) data.WOS:0007185529000012-s2.0-8512037781

Conventional and microwave irradiated synthesis, biological activity evaluation of highly substituted indole-triazole hybrids

In the present study, a series of new indole-3-carbaldehyde embedded triazole derivatives have been synthesized. 4-{[(1E)-1H-indol-3-ylmethylidene]amino}-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (2) were converted to the corresponding Mannich bases containing flouroquinolone core via a one-pot, three-component reaction. The synthesis of conazole analogues was carried out starting from triazoles by three steps. Reactions were carried out under conventional and microwave-mediated conditions. Various catalysts and solvents were tested to see how they affected conventional and microwave (MW)-induced reactions. The antibacterial characteristics of all the newly synthesized compounds were tested, and the majority of them showed good to moderate activity. The most significant result of our investigation is the high activity of fluoroquinolone derivative compounds that we synthesized as hybrid molecules

An efficient microwave-assisted synthesis of novel quinolone-triazole and conazole-triazole hybrid derivatives as antimicrobial and anticancer agents

1,2,4-Triazole-fluoroquinolone and 1,2,4-triazole–conazole hybrids aredesigned, synthesized, and investigated in vitro against a variety of commondiseases. The structure of the newly synthesized compounds are characterizedfrom spectral data (IR,1H NMR,13C NMR, and LC–MS). The antibacterialactivity against both Gram-positive and Gram-negative bacteria is shown to beenhanced by many of the produced compounds. Also, some of the productsare found to have strong antiproliferative effects aganist HeLa cervical cancercells, whilst demonstrating cytotoxic effects toward normal cell

Conventional and microwave-assisted synthesis of novel 1,2,4-triazole derivatives containing tryptamine skeleton and evaluation of antimi-crobial activity

1,2,4-Triazole-3-one (3) obtained from tryptamine was transformed to the corresponding car-box(thio)amides via several steps (6a-d). Their reaction with sodium hydroxide performed the 1,2,4-triazole derivatives (7a-d). Compounds 7a-d treatment by 2-bromo-1-(4-chlorophenyl)ethanoneain an ambiance with sodium ethoxide afforded the compounds (8a-d). The reduction reaction of 8a-d afforded 1,2,4-triazoles (9a-d). The synthesis of (10a-d), (11a-d) and (12a-d) was afforded treatment of products 9a-d with 4-chlorobenzyl chloride (for 10a-d) or 2,6-dichlorobenzyl chloride (for 11a-d) or 2,4-dichlorobenzyl chloride (for 12a-d). Besides the improved of entirely novel agents having various chemical features than those of the existing ones, another aim is to combined two or more groups into a single hybrid compound. For this reason, a single compound containing more than one group, each with various modes of effect, could be helpful for the cure of bacterial infections. Microwave-assisted and conventional techniques were utilized for the syntheses. The structures of recently obtained molecules were elucidated on the foundation of1H NMR,13C NMR, FT IR, EI MS methods and elemental analysis. All novel synthesized molecules were investigated for their antimicrobial activity using MIC (minimum inhibitory concentration) method. The aminoalkylation of triazoles (7a-d) formed products 8a-d which have excellent activity against testing bacteria with values between 0.24 and 125 µg/mL. Especially compounds 8a and 8d exhibited much better activity against E. coli than ampicillin used as standard drug. The microwave process ensured a more efficient road to the creation of desired mole-cules. The antibacterial examination demonstrated that after the carbonyl group is increased the anti-bacterial activity of the compounds is greatly increased. That's why molecules formed as a result of the alkylation reactions of triazoles has high activity

Synthesis of novel antipyrine-azole-S-alkyl derivatives antimicrobial activity, molecular docking, and computational studies

In this investigation, we synthesized the newly antipyrine-azole-S-alkyl and their reduction derivatives that were screened for their antimicrobial activity and compared them with molecular docking and computational Studies. The nucleophilic substitution reaction between antipyrine-azole derivatives 1a, 1b and (2,4-dichlorophenyl) acetyl chloride ( 2 ) in presence of Na metal to afforded the corresponding 2-(2,4-dichlorophenyl)-2-oxoethyl)thio)-4H-1,2,4-triazol-3-yl)methyl)amino)-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one derivatives 3a, 3b in excellent yield. The reduction process of compounds 3a,3b were utilized via NaBH4 act as reducing agent which convert the C = O group to OH group to afford the corresponding 2-(2,4-dichlorophenyl)-2-hydroxyethyl)thio)-4H-1,2,4-triazol-3-yl)methyl)amino)-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one derivatives 4a, 4b. The investigated compounds were exhibited against in vitro antimicrobial activity. Compound 3a was determined to be the most effective against all strains. In addition, it was observed that compound 4a showed very good antitubercular activity ( Mycobacterium smegmatis ATCC607) and showed equivalent activity to Staphylococcus aureus ATCC 25923 against the standard drug from gram-positive bacteria. Compound 3b with allyl group in its structure was found to be effective against Pseudomonas aeruginosa ATCC 27853, one of the gram-negative bacteria. Furthermore, molecular docking studies were carried out on one of the investigated compounds with (PDB ID:3t88), (PDB ID:2wje), (PDB ID:4ynt), and (PDB ID:1tgh), which attached with different proteins with different energies and short bond distance. Furthermore, the comprehensive theoretical and physical characterization studies of compounds 3a, 3b,4a, and 4b were examined via DFT/ B3LYP/6-31 G (d) level to elucidate their activities. (C)& nbsp;2022 Elsevier B.V. All rights reserved.Scientific Research Project of Karadeniz Technical University (KTU-BAP) FBB-2015-528

Microwave-assisted synthesis of novel mannich base and conazole derivatives containing biologically active pharmacological groups

Background: The aim of this study was to synthesize new Mannich bases and conazol derivatives with biological activity by the microwave-assisted method. Introduction: 1,2,4-Triazole-3-one (3) acquired from tryptamine was transformed to the corresponding carbox(thio)amides (6a-c) via several steps. Compounds 6a-c were refluxed with sodium hydroxide to yield 1,2,4-triazole derivatives (7a-c). Compounds 3 and 7a-c on treatment with different heterocyclic secondary amines in an ambiance with formaldehyde afforded the Mannich bases 8-15 having diverse pharmacophore units with biologically active sites. The reaction of compound 3 and 2-bromo-1-(4-chlorophenyl) ethanone in the presence of sodium ethoxide gave the corresponding product 2-substituted-1,2,4-triazole-3-one, 16, which was reduced to 1,2,4-triazoles (17). Synthesis of compounds 18, 19, and 20 was carried out starting from compounds 17 with 4-chlorobenzyl chloride (for 18), 2,4-dichlorobenzyl chloride (for 19), and 2,6-dichlorobenzyl chloride (for 20). Methods: The conventional technique was utilized for the synthesis of compounds, 3-7, and microwave-assisted technique for the compounds, 8-20. That is, green chemistry techniques were applied during these reactions. The structures of molecules were elucidated on the foundation of 1H NMR, 13C NMR, FT-IR, EI-MS methods, and elemental analysis. Novel synthesized molecules were investigated for their antimicrobial activity using MIC (minimum inhibitory concentration) method. Results: Aminoalkylation of triazole derivatives 3 and 7a-c with fluoroquinolones such as ciprofloxacin and norfloxacin provided an enhancement to the bioactivity of Mannich bases 8-11 against the tested microorganisms. The MIC values ranged between <0.24 and 3.9 μg/mL. Moreover, molecules 10 and 11 exhibited more effects on M. smegmatis than the other compounds by the MIC values of <1 μg/mL. They have shown very good antituberculosis activity. Conclusion: Most of the synthesized structures were observed to have excellent antimicrobial activity against most microorganisms taken into account. These molecules have better activity than the standard drug ampicillin and streptomycin