Synthesis and antimicrobial screening of 4-thiazolidinone and 2-azetidinone derivatives of piperazine

The Schiff’s bases 3a–3h were synthesized by reacting substituted/unsubstituted aromatic aldehydes 2a–2h with 1-(2-aminoethyl)-piperazine 1. A series of novel aryl-3-(2-piperazin-1-ylethyl)-1,3-thiazolidin-4-one 4a–4h and 3-chloro-1-{2-[4-(chloroacetyl)piperazin-1-yl]ethyl}-4-arylazetidin-2-one 5a–5h were synthesized from the Schiff’s bases of 1-(2-aminoethyl)-piperazine 3a–3h. The structures of synthesized compounds were confirmed by analytical (C, H, and N) and spectral (FT-IR, ¹H NMR, ¹³C NMR, and Mass) data. The compounds 4a–4h and 5a–5h were screened for antimicrobial activity. The compounds 4a, 4d, 4f, 4g, 5a, 5d, 5f, and 5g exhibited substantially significant antibacterial as well as antifungal activity.     

Synthesis of some novel C-5 and N-3 substituted 2-(2-hydroxyphenylimino)thiazolidin-4-one derivatives with broad-spectrum antimicrobial activity

In the present article, compounds 5-((substituted-2-chloroquinolin-3-yl)methylene)-2-(2-hydroxyphenylimino)thiazolidin-4-ones (3a–k), 1-(2-(2-(2-hydroxyphenylimino)-4-oxothiazolidin-3-yl)-2-oxoethyl)pyrimidine-2,4,6(1H,3H,5H)-trione (6) and 1-(2-(5-((substituted-2-chloroquinolin-3-yl)methylene)-2-(2-hydroxyphenylimino)-4-oxothiazolidin-3-yl)-2-oxoethyl)pyrimidine-2,4,6(1H,3H,5H)-triones (8a–k) have been synthesized by substituting C-5 and N-3 position of parent compound 2-(2-hydroxyphenylimino)thiazolidin-4-one (1). Structures of the newly synthesized compounds were assigned on the basis of elemental analyses, IR, ¹H NMR, ¹³C NMR, and mass spectra. In vitro antimicrobial activity of target compounds (3a–k, 6 and 8a–k) was investigated against two Gram-positive, two Gram-negative bacteria and three fungal strains. Among the tested compounds (3e), (3f), and (3h) showed very good antifungal activity, while compound (6) showed very good antibacterial activity. Compounds (8e), (8f), and (8h) showed excellent antifungal and antibacterial activities.     

Synthesis of azabicyclo[4.2.0]octa-1,3,5-trien-8-one analogues of 1H-imidazo[4,5-c]quinoline and evaluation of their antimicrobial and anticancer activities

In search of new and efficient antimicrobial and anticancer agents based on the imidazoquinoline structural framework, a series of novel 7-(1-isobutyl-1H-imidazo[4,5-c]quinolin-4-yl)-7-azabicyclo[4.2.0]octa-1,3,5-trien-8-ones (8a–f) were synthesized from the corresponding 2,4-dihydroxoquinoline derivative through multistep reactions. The structures of these compounds were established by IR, ¹H NMR, ¹³C NMR and mass spectral studies. The 7-(1-isobutyl-1H-imidazo[4,5-c]quinolin-4-yl)-7-azabicyclo[4.2.0]octa-1,3,5-trien-8-one (8a–f) analogues were evaluated for their in vitro antimicrobial activity by serial dilution method minimum inhibitory concentration (MIC). The derivatives 8c, 8e and 8f exhibited excellent antibacterial activity comparable to the parent drug ampicillin with MIC value. Compounds 7a–f and 8a–f were also assessed for their cytotoxic activity (IC₅₀) against HeLa cells using the Trypan blue exclusion assay method. The compounds 7c and 8b displayed potential anticancer activity. In a molecular docking study, these compounds showed minimum binding energy and good affinity towards the active pocket. They are believed to be good inhibitors of β-tubulin. The results of these studies provided evidence that 7-(1-isobutyl-1H-imidazo[4,5-c]quinolin-4-yl)-7-azabicyclo[4.2.0]octa-1,3,5-trien-8-one (8a–f) derivatives are a promising class of antibacterial and anticancer agents.     

Synthesis and antimicrobial activity of bischalcone derivatives

Several bischalcones (2a–h and 5a–e) and flavones (3a–f) were synthesized and evaluated for their antimicrobial actions. Bischalcones were prepared by condensing 1,1′-(4,6-dimethyl-1,3-phenylene)diethanone (1) or 1-(5-acetyl-2,4-dimethoxyphenyl)-1-ethanone (4) with arylaldehydes. Bischalcones were cyclized in presence of iodine to give corresponding flavones (3a–f). An alternative route to synthesize the flavones consisted in preparing the diester derivatives (6a–f) of (1) with different aromatic acids, which could be converted to β-diketones followed by cyclization to give the corresponding flavones. However, all the attempts in this direction were unsuccessful and it could not be possible to proceed beyond diester stage; six diester derivatives (6a–f) were synthesized. The structures of the synthesized compounds were assigned on the basis of ¹H NMR, mass spectral data and microanalyses results. The antimicrobial screening was performed at a concentration of 100 μg/mL by cup plate method; the compounds inhibiting growth of one or more of the microorganisms were further tested for their minimum inhibitory concentration (MIC) by turbidity method. Preliminary antimicrobial results revealed that the compounds 2a–h and 3a–f were significant in their antibacterial and antifungal activities. MICs results showed that the compound 2f exhibited very good activity against E. coli, P. aeruginosa, and C. albicans with MIC-12.5 μg/mL. Similar type of activity was shown the compound 3a against S. aureus and C. albicans with MIC-12.5 μg/mL. Another compound, 3f, was active against P. aeruginosa and C. albicans with MIC-12.5 μg/mL. Methylation of the two chelated hydroxyls (5a–e) significantly reduced the activity. However, oxidative cyclization of bischalcones resulted in compounds (3a–f) which were found to be considerably active. Diesters (6a–f) were insignificant in their antimicrobial activities.     

Synthesis and antimicrobial activity of 5-chloroindoline-2,3-dione derivatives

A series of 3-(5-chloro-2-oxoindolin-3-ylideneamino)-2-arylthiazolidin-4-ones 4a–k and 5-chloro-3-(3-chloro-2-oxo-4-arylazetidin-1-ylimino)indolin-2-ones 5a–k was synthesized. The structures of final compounds were confirmed by analytical (C, H, N) and spectral (FT-IR, ¹H NMR, ¹³C NMR and Mass) data. The synthesized compounds were screened for possible antibacterial and antifungal activity. Compounds 4c, 4f, 4g, 4h, 4i, 4j, 5c, 5f, 5g, 5h, 5i and 5j showed substantially significant activity.     

Synthesis,antimicrobial, and antioxidant activity of benzofuran barbitone and benzofuran thiobarbitone derivatives

The synthesis of novel series of benzofuran derivatives, containing barbitone moiety, 5-[(2/4-substitutedphenyl)(5-substituted-1-benzofuran-2-yl) methylidene]pyrimidin-2,4,6(1H,3H,5H)-trione (4a–i) and thiobarbitone moiety, 5-[(2/4-substitutedphenyl)(5-substituted-1-benzofuran-2-yl)methylidene]-2-thioxodihydropyrimidin-4,6(1H, 5H)-dione (5a–i) have been reported. The target compounds (4a–i) and (5a–i) were synthesized by the Knoevenagel condensation of (5-substituted-1-benzofuran-2-yl)(2/4-substitutedphenyl) methanone (3a–i) with barbituric acid and thiobarbituric acid, respectively, in acid medium. These compounds were screened for the antimicrobial and antioxidant activities. From antimicrobial activity results it was found that compounds 4a, 5a, 4c, and 5c displayed good antibacterial and antifungal activity against all tested strains. Further, the synthesized compounds were studied for docking on the enzyme, Glucosamine-6-phosphate synthase and the compounds 4c and 5c have emerged has an active antimicrobial agent with least binding energy (?5.27 and ?4.85 kJ mol^?1). Compounds 4e, 4f, 5e, and 5f showed promising free radical scavenging activity and compounds 5a and 5b showed good chelating ability with Fe²⁺ ions.     

Synthesis, characterization, and antimicrobial evaluation of novel naphthalene-based 1,2,4-triazoles

In order to search for new bioactive molecules with significant antimicrobial action, a series of 1,2,4-triazole and naphthalene analogs bearing structurally diverse substituents, N-(3-mercapto-5-(naphthalen-1-yl)-4H-1,2,4-triazol-4-yl)(aryl)amides 3a–l were synthesized in good yield by a multi-step synthetic procedure. Their antimicrobial activity was screened against various Gram-positive and Gram-negative bacteria and fungi. Compounds 3a, 3f, 3g, 3j, and 3k exerted strong inhibition of the investigated bacterial and fungal strains compared to control antibiotic ampicillin and antifungal griseofulvin. On the basis of statistical analysis, it is observed that the compounds give significant co-relation. All the synthesized compounds have been characterized by IR, ¹H NMR, ¹³C NMR, and mass spectral data.     

Synthesis and in vitro antitumor activity of new quinoline, pyrimido[4,5-b]quinoline, [1,2,3]triazino[4,5-b]quinoline, and [1,2,4]triazolo[2′,3′:3,4]pyrimido[6,5-b]quinoline analogs

New series of quinoline, pyrimido[4,5-b]quinoline, [1,2,3]triazino[4,5-b]quinoline, and [1,2,4]triazolo[2′,3′:3,4]pyrimido[6,5-b]quinoline analogs have been synthesized and characterized by analytical and spectrometrical methods (IR, ¹H NMR, ¹³C NMR, MS). Fifteen of the newly synthesized compounds; namely, 3a, b, 4b, 6a, b, 10a–f, and 14a–d were evaluated for their in vitro antitumor activity at the National Cancer Institute (NCI) 60 cell lines panel assay. Compounds 4b and 10f are the most active members in this study, demonstrating significant broad spectrum antitumor activity against most of the tested sub-panel tumor cell lines. The detailed synthesis, spectroscopic, and biological data are described.     

An efficient, solvent-free microwave-assisted synthesis and antimicrobial screening of 1,6-dihydropyrimidine analogues

A series of compounds 4-(4-(4-aminophenyl)-6-(aryl)-1,6-dihydropyrimidin-2-ylthio)butanenitriles 5a–l were synthesised by the reaction of allyl cyanide 4 with 3a–l. Compounds 3a–l were prepared from reaction between various chalcones 1a–l and thiourea in presence of catalytic amount of potassium hydroxide. Compounds 3a–l, and 5a–l were prepared by classical as well as MWI methods. Structures of the compounds were characterized by IR, ¹H NMR, ¹³C NMR and mass spectral data. The newly synthesized compounds 5a–l were screened for their antimicrobial activity against different strains of bacteria and fungi using serial broth dilution method. Compounds 5e, 5g and 5k were found to be most active with MIC of 25?μg/mL against selected bacterial strains, while compound 5d, 5f, 5j and 5k were found to be most active with MIC 50?μg/mL against selected fungal strains.     

Synthesis of benzothiazole derivatives having acetamido and carbothioamido pharmacophore as anticonvulsant agents

A new series of N-(6-chlorobenzothiazol-2-yl)-2-substituted-acetamides (3a–h) and N-(6-chlorobenzothiazol-2-yl)-2-(substituted-benzylidene)hydrazinecarbothioamides (5a–h) were synthesized and characterized by IR, ¹H NMR, mass and elemental analysis. In vivo anticonvulsant and acute toxicity screening of all the synthesized compounds showed morpholino (3f) and imidazolyl (3g) derivatives as promising anticonvulsant lead. Furthermore, In silico drug-likeness parameters have also been investigated for filtering out the likelihood of poor drug absorption or brain penetration. 3D four-point pharmacophore measurements of compounds were also carried out to match these with established anticonvulsants agents.     

Synthesis, characterization, and in vitro antimicrobial evaluation of new 5-chloro-8-bromo-3-aryl-1,2,4-triazolo[4,3-c]pyrimidines

A series of new 5-chloro-8-bromo-3-aryl-1,2,4-triazolo[4,3-c]pyrimidines (4a–j) have been accomplished in excellent yields by the oxidative cyclization of pyrimidinylhydrazines (3a–j) of various aryl aldehydes with one equivalents of iodobenzene diacetate in methanol. The chemical structures of the synthesized compounds were confirmed by elemental analyses, FT-IR, ¹H NMR, ¹³C NMR, and mass spectral studies. Ten new compounds (4a–j) were tested in vitro for their antimicrobial activity against clinically isolated strains. Variable and modest activities were observed against the investigated strains of bacteria and fungi. Compounds 4f, 4i, and 4j demonstrated good antimicrobial activity against all the tested microbial strains.     

Antimicrobial and antiquorum-sensing studies. Part 2: synthesis, antimicrobial, antiquorum-sensing and cytotoxic activities of new series of fused [1,3,4]thiadiazole and [1,3]benzothiazole derivatives

New series of [1,3,4]thiadiazolo[3,2-a]pyrimidines, [1,3,4]thiadiazolo[2,3-b]quinazolines, and pyrimido[2,1-b][1,3]benzothiazoles have been synthesized and characterized by analytical and spectrometrical methods (IR, MS, ¹H, and ¹³C NMR). Sixteen of the synthesized compounds; namely, 3a, b, 5a–f, 8a, b, 10, 11a–c, and 13a, b were screened for antibacterial activity against Escherichia coli, Staphylococcus aureus, and Bacillus cereus. They were found to be either moderately active, slightly active or inactive against the selected microorganisms. The antifungal activity of these compounds were also tested against Candida albicans, Aspergillus fumigatus 293, and Aspergillus flavus 3375. Compound 11a showed potent antifungal activity against the three selected fungi; the rest of the tested compounds displayed either weaker activity or were completely inactive. The same compounds were examined for antiquorum-sensing activity against Chromobacterium violaceum ATCC 12472, where compounds 3a, 10, 11a, and 13a, b exhibited promising activity. The in vitro cytotoxic activity of these compounds was also studied by brine shrimp lethality bioassay, and results indicated that compounds 3a, 11a, and 13a have the highest cytotoxic activity.     

Synthesis,antimicrobial, and cytotoxic activities of novel benzimidazole derivatives bearing cyanopyridine and 4-thiazolidinone motifs

A series of 6-(1H-benzo[d]imidazol-2-yl)-2-(2-(3-nitrophenyl)-4-oxothiazolidin-yl)-4-(aryl)nicotinonitriles 5a–l were synthesized and characterized by IR, ¹H NMR, ¹³C NMR, and mass spectrometry techniques. These novel compounds 5a–l were screened for their in vitro antimicrobial activity against different bacterial and fungal strains and in vitro cytotoxicity study (HeLa cell line) using MTT colorimetric assay. The results demonstrated that compounds 5c, 5e, and 5i–k exhibited excellent antibacterial activity, while compounds 5d, 5i, and 5k were found to be the most potent antifungal agents. From the standpoint of SAR studies, it was observed that the presence of electron donating groups remarkably enhanced the antimicrobial activity of newly synthesized compounds. Further, the results of preliminary MTT cytotoxicity studies on HeLa cells suggested that potent antimicrobial activity of 5c–e and 5i–k was accompanied by low cytotoxicity.     

Synthesis and antimicrobial activity of coumarin pyrazole pyrimidine 2,4,6(1H,3H,5H)triones and thioxopyrimidine4,6(1H,5H)diones

A series of 5-((3-(2-oxo-2H-chromen-3-yl)-1-phenyl-1H-pyrazol-4-yl)methylene)pyrimidine-2,4,6(1H,3H,5H)-trione (4a–f) and dihydro-5-((3-(2-oxo-2H-chromen-3-yl)-1-phenyl-1H-pyrazol-4-yl)methylene)-2-thioxopyrimidine-4,6(1H,5H)-dione (5a–f) derivatives were synthesized by the condensation of 3-(2-oxo2H-chromen-3-yl)-1-phenyl-1H-pyrazole-4-carbaldehyde (3a–f) with barbituric acid and thiobarbituric acid in acetic acid under microwave irradiation method. The newly synthesized compounds were evaluated for their antibacterial activity against Bcillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeoginosa, and Klebsiella pneumoniae. All the compounds were found to be moderately active against used microorganisms, whereas compounds (4d) and (4e) exhibited good antifungal activity against Aspergillus niger.     

Zn(OTf)2-catalyzed three component, one-pot cyclocondensation reaction of some new octahydroquinazolinone derivatives and access their bio-potential

An efficient synthesis of some new octahydroquinazolinone derivatives 4a–x by the cyclocondensation reaction of corresponding 2-thi(oxo)-1,2-dihydroquinoline-3-carbaldehyde 1a–e, 1,3-dicarbonyl compounds 2a–b, and substituted urea 3a–c using zinc triflate as a catalyst in refluxing ethanol in high yield is described. The structures of new compounds have been characterized on the basis of elemental analysis, FT- IR, ¹H NMR, ¹³C NMR, and mass spectral data. All the synthesized compounds were evaluated for their antimicrobial activities against various microbes. Minimum inhibitory concentration values of all the 24 synthesized compounds were also determined. Some of the synthesized compounds exhibited excellent antimicrobial activity.     

Synthesis and pharmacological evaluation of some novel 4-isopropyl thiazole-based sulfonyl derivatives as potent antimicrobial and antitubercular agents

A series of novel sulfonyl derivatives 3-(substituted benzylsulfonyl)-5-(4-isopropylthiazol-2-yl)-4-phenyl-4H-1,2,4-triazoles 4a–4e, isopropyl thiazole-derived schiff bases 8a–8l, and 2-(substituted benzylsulfonyl)-5-(4-isopropylthiazol-2-yl)-1,3,4-oxadiazoles 11a–11e were synthesized and characterized by IR, ¹H NMR, ¹³C NMR, elemental, and mass spectral analysis. All the compounds exhibited moderate to significant antibacterial and antifungal activities. Results of the antitubercular screening against Mycobacterium tuberculosis H37Rv ascertain compounds 4e, 8b, and 8f as excellent antitubercular molecules, when compared with first line drug isoniazid (0.25 μg/mL).     

Synthesis and evaluation of analgesic, anti-inflammatory, and anticancer activities of new pyrazole-3(5)-carboxylic acid derivatives

In this article, we synthesized a series of novel 1-benzyl-5(3)-p-tolyl-1H-pyrazole-3(5)-carboxylic acid derivatives and characterized by IR, ¹H NMR, and mass spectroscopy. Compounds were evaluated for their in vivo analgesic and anti-inflammatory activity using the p-benzoquinone-induced writhing test and the carrageenan-induced paw edema model, respectively. Out of 14 compounds tested, 7a, 7c, 7e, 7f, 7i, 8a–b, and 8f–g exhibited potent analgesic and/or anti-inflammatory activity as compared to reference drugs aspirin and indomethacin. Anticancer activity of these compounds was assessed against five cancer cell lines with the MTT assay (HL-60, human promyelocytic leukemia cells; HeLa, human cervical cancer cells; Raji, human B lymphocyte cell line; MCF7, human breast adenocarcinoma cell line; MDA-MB-231, estrogen-independent human breast cancer cell line). Compounds 7a, 8a, and 8b with high anti-inflammatory activity, and also 7d and 7j with mild anti-inflammatory activity exhibited promising anticancer activity against some selected cell lines.     

Design, synthesis, and preliminary in vitro and in vivo pharmacological evaluation of 4-{4-[2-(4-(2-substitutedquinoxalin-3-yl)piperazin-1-yl)ethyl]phenyl}thiazoles as atypical antipsychotic agents

A series of 4-{4-[2-(4-(2-substitutedquinoxalin-3-yl)piperazin-1-yl)ethyl] phenyl} thiazoles were synthesized in an effort to prepare novel atypical antipsychotic agents. The compounds were designed, synthesized, and characterized by spectral data (IR, ¹H NMR, and MS) and the purity was ascertained by microanalysis. The D₂ and 5-HT_2A affinity of the synthesized compounds was screened in vitro by radioligand displacement assays on membrane homogenates isolated from rat striatum and rat cortex, respectively. Furthermore, all the synthesized final compounds (10a–g; 11a–g; 12a–g) were screened for their in vivo pharmacological activity in Swiss albino mice. D₂ antagonism studies were performed using climbing mouse assay model and 5-HT_2A antagonism studies were performed using quipazine-induced head twitches in mice. It was observed that none of the new chemical entities exhibited catalepsy and 12d, 11f, and 10a were found to be the most active compounds with 5-HT_2A/D₂ ratio of 1.23077, 1.14286, and 1.12857, respectively, while the standard drug risperidone exhibited 5-HT_2A/D₂ ratio of 1.0989. Among the twenty one new chemical entities, three compounds (12d, 11f, and 10a) were found to exhibit better atypical antipsychotic activity as they were found to have higher Meltzer index than the standard drug risperidone.     

Synthesis of new oxadiazole derivatives as anti-inflammatory, analgesic, and antimicrobial agents

In search of pharmalogically active molecules in the class of oxadiazoles, the present article deals with the synthesis of 5-(5′-fluoro-2′-methoxybiphenyl-3-yl)-1,3,4-oxadiazol-2(3H)-one 2 from its hydrazide analog 1. The compound 2 was regioselectively N-alkylated with alkyl halides and produced the compounds 3a–f. Compound 3f was further functionalized with substituted benzenesulfonyl chlorides to give compounds 3g–j. The synthesized compounds were characterized by elemental and spectral analysis. Newly synthesized compounds were tested for their in vivo anti-inflammatory, analgesic, and in vitro antimicrobial activities. The compounds 3a–c were found to have promising anti-inflammatory and analgesic activities. Compounds 3b, 3f, and 3g showed significant antibacterial and antifungal activities.     

New 4-thiazolidinones from 5-ethyl pyridine-2-ethanol: their antibacterial,antifungal, and antitubercular activity

New thiazolidinones 5a–o were prepared from Schiff base 4a–o and thioglycolic acid in the presence of ZnCl₂ from 4-[2-(5-ethylpyridin-2-yl)ethoxy]benzaldehyde. The structures of the synthesized compounds were assigned on the basis of elemental analysis, IR, ¹H NMR ¹³C NMR, and mass spectral data. All the compounds were screened against different strains of bacteria and fungi. Compounds 4e, 4n, 4m, 4o, 5e, 5f, 5j, and 5m possessed very good activity against bacterial and fungal species. These active compounds impelled us to study their antitubercular activity. Schiff base 4n and 4e showed M. tuberculosis MIC value 25 and 62.5 μg/ml, respectively. Thiazolidinone 5m displayed M. tuberculosis MIC at 25 μg/ml, which is better antitubercular activity compared with rifampicin.