Synthesis and antitubercular activity of novel pyrazole–quinazolinone hybrid analogs

A series of 2-(substituted-phenyl)-3-(((3-(pyridin-4-yl)-1-(p-tolyl)-1H-pyrazol-4-yl)methylene)amino)-quinazolin-4(3H)-ones have been synthesized. The structures of the synthesized compounds were assigned on the basis of IR, ¹H NMR, ¹³C NMR, and mass spectral data, while their abilities to inhibit growth of Mycobacterium tuberculosis in vitro have been determined. The results show that compounds 5a, 5c, 5d, 5g, and 5k exhibited excellent antitubercular activity with percentage inhibition of 96, 90, 94, 93, and 92, respectively at a minimum inhibitory concentration (MIC) of <6.25 μg/mL, whereas compounds 5b, 5e, 5f, 5h, 5i, 5j, and 5l exhibited moderate- to- good antitubercular activity with percentage inhibition of 68, 70, 67, 64, 59, 73, and 67, respectively, at a MIC of >6.25 μg/mL. From the secondary screening, the actual MIC of compounds 5a, 5c, 5d, 5g, and 5k are <3.125.     

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, anti-inflammatory, and cytotoxicity evaluation of 9,10-dihydroanthracene-9,10-α,β-succinimide and bis-succinimide derivatives

9,10-Dihydroanthracene-9,10-α,β-succinimide derivatives 4a–e and bis-succinimide derivatives 6a–e have been synthesized by grinding 9,10-dihydroanthracene-9,10-α,β-succinic anhydride 2 with various mono 3a–e and diamines 5a–e in quantitative yields. All the target compounds were fully characterized by spectrometric and spectroscopic means. Compounds 4a–e, 6a–e and recently reported compounds 4f–p were screened for anti-inflammatory and for cytotoxicity against five human cancer cell lines: T47D, NCI H-522, HCT-15, PA1, and HepG-2. Compounds 4e, 4i, 4j, and 4p exhibited good anti-inflammatory activity and compounds with interesting cytotoxic profile were 4c, 6e (T47D); 4e, 4o (NCI H-522); 4n (HCT-15); 4e, 4h, 4o (PA1); and 4a, 4e, 4f, 4i, 4o (HepG-2).     

Synthesis, characterization and antimicrobial studies of a few novel thiazole derivatives

A series of novel N-[4-(substituted)-1,3-thiazol-2-yl]-2-(substituted)acetamide (9a–m) and methyl 2-(2-(2-(substituted)acetamido)thiazol-4-yl)acetate (9n–o) derivatives have been synthesized and compounds were characterised by spectral and analytical studies. All compounds were screened for their in vitro antibacterial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumonia by disc diffusion method and for antifungal activity against Penicillium marneffei, Trichophyton mentagrophytes, Aspergillus flavus and Aspergillus fumigatus by serial plate dilution method. Compounds 9b, 9e, 9m and 9o exhibited growth inhibition against all the tested bacterial strains, with MIC values varying from 12.5 to 6.25 μg/ml. Among the compounds tested for antifungal activity, 9a, 9b, 9d, 9j, 9k, 9p and 9n showed wide range of activity against all the tested strains. Most of the newly synthesized compounds were effective against fungal strains rather than bacterial strains. However, some of the compounds like 9a, 9e, 9j, 9k and 9i showed selective sensitivity against some of the bacterial strains whereas they were unable to sustain the growth of other strains.     

Anti-mycobacterial, cytotoxic activities of Knoevenagel and (E)-α,β-unsaturated esters and ketones from 2-chloronicotinaldehydes

Series of 2-chloronicotinaldehyde Knoevenagel derivatives 3a–r; (E)-α,β-unsaturated esters and ketones 5a–k were prepared and evaluated for their in vitro anti-mycobacterial activity against Mycobacterium tuberculosis H₃₇Rv (Mtb). Compounds 3e, 5b, 5d, 5e, 5g and 5i–k were shown potent to significant activity. Compound 5j is the most potent Mtb inhibitor (MIC: 4.89 μM) when compared to standard drugs Ethambutol (MIC: 7.63 μM) and Ciprofloxacin (MIC: 9.44 μM). Eight compounds displayed potent/significant activity against M. tuberculosis were chosen for the cytotoxicity against three cell lines (Raw 264.7, MCF7, and HeLa). Compound 5j displayed low toxicity with high selective index (15–30) and is an interesting new compound may serve for the development of therapeutics targeted against anti-mycobacterial compounds. This is the first report assigning in vitro anti-mycobacterial inhibitory activity and structure–activity relationship for this class of substituted 2-chloronicotinaldehyde derivatives and presents new family of compounds.     

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.     

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 and anti-tubercular evaluation of some novel pyrazolo[3,4-d]pyrimidine derivatives

A series of phenothiazine clubbed pyrazolo[3,4-d]pyrimidines have been synthesized by using the Biginelli multi-component cyclocondensation reaction and their ability to inhibit growth of Mycobacterium tuberculosis in vitro have been determined. The results show that compounds 4b, 4d, and 4f exhibited excellent anti-tubercular activity with percentage inhibition of 93, 91, and 96, respectively, at a minimum inhibitory concentration (MIC) of <6.25?μg/ml, whereas compounds 4a, 4c, 4e, 4g, and 4h exhibited moderate to good anti-tubercular activity with percentage inhibition of 75, 68, 74, 54, and 63, respectively at a MIC of >6.25?μg/ml.     

Synthesis and pharmacological evaluation of novel 4-isopropylthiazole-4-phenyl-1,2,4-triazole derivatives as potential antimicrobial and antitubercular agents

A series of novel 4-isopropylthiazol-4-phenyl-1,2,4-triazol derivatives, N′-(substituted benzylidene)-2-(5-(4-isopropylthiazol-2-yl)-4-phenyl-4H-1,2,4-triazol-3-ylthio)acetohydrazides 4a–e, 4-isopropylthiazol-2-yl-4′-phenyl-4′H-1′, 2′,4′-triazol-3′-ylthio (substituted methyl benzylidene) acetohydrazides 5a–f, 3-(4-isopropylthiazol-2-yl)-4-phenyl-5-(5-substituted-1,3,4-oxadiazol-2-ylthio)-4H-1,2,4-triazole derivatives 6a–f and N-acetyl-5′-(4-isopropylthiazol-2-yl)-4′-phenyl-4′H-1,2,4-triazol-3′-ylthio) acetohydrazide 7 were synthesized and characterized by spectroscopy, elemental, and mass spectral analysis. These compounds were evaluated for their preliminary in vitro antibacterial, antifungal, and antitubercular activity against Mycobacterium tuberculosis (M. tuberculosis) H37Rv strain by broth dilution assay method. All the compounds exhibited moderate to significant antibacterial and antifungal activities. Results of the antitubercular screening against Mycobacterium tuberculosis H37Rv showed that compounds 4c and 6c exhibited good antitubercular activity when compared with first line drug isoniazid.     

Synthesis and biological evaluation of novel curcumin analogues as anti-inflammatory, anti-cancer and anti-oxidant agents

A series of novel curcumin analogues 5a–m were synthesized by Claisen-Schmidt condensation of various aromatic and heteroaromatic amides of 3-aminoactophenones 4a–m with 3-bromo-2,4,6-trimethoxybenzaldehyde and characterized by IR, ¹H NMR and mass spectroscopic analysis and were evaluated for anti-inflammatory, anti-cancer and anti-oxidant activity. Out of the 13 synthesized compounds, compounds 5f, 5j and 5m were excellent inhibitors of TNF-α and IL-6. Compounds 5c, 5e, 5b and 5d showed potent COX-2 inhibition, compounds 5d and 5f have shown good trypsin inhibition and compounds 5e, 5g and 5c exhibited excellent β-glucuronidase inhibition. Compounds 5l and 5m showed potent anti-cancer activity against selected five human cancer cell lines. All the compounds exhibited moderate free radical scavenging activity, while compounds 5a and 5m were excellent OH radical scavengers.     

Design, synthesis and in vitro antimicrobial activity of novel phenylbenzamido-aminothiazole-based azasterol mimics

Phenylbenzamide framework as a mimic of the azasterol structure was investigated by synthesizing 4-phenylbenzamido-2-aminothiazole 4, and evaluating its MIC against Escherichia coli, Enterobacter cloacae, Bacillus licheniformis and Mycobacterium tuberculosis (MTB) H₃₇Rv as well as antifungal activity against three test phytopathogenic fungi. Further, the bioisosterism strategy was implemented to synthesize a series of azo-derivatives of 4 (6a–6j). All the azo-compounds were screened for their antibacterial and antifungal activity. The electronic (UV–vis) absorption characteristics of the final compounds were examined. Resazurin-mediated microtitre plate-antibacterial assay was implemented for first time on these azo-derivatives. Compounds 4 and 6b had significant antibacterial activity. For the compound 4, MIC against Escherichia coli is 7.8 × 10^?3 mg/mL and MIC against Mycobacterium tuberculosis (MTB) H₃₇Rv is 16 μg/mL were identified. Compounds 4, 6d, 6g and 6h showed excellent antifungal activity, when compared to the standard nistatin, against three test phytopathogenic fungi.     

Newer thiazolopyrimidine-based sulfonamides clubbed with benzothiazole moiety: synthesis and biological evaluation

A new class of thiazolopyrimidine-based sulfonamides (5a–j) was synthesized from a parent compound 2-methoxy benzoic acid by multistep reaction in order to find new agents to fight against microbial infections. Substituted thiazolopyrimidines (3a–e) were prepared by cyclocondensation of substituted thiazolidinediones (2a–e) with urea in the presence of acid catalyst P₂O₅. Finally, desired compounds (5a–j) were synthesized from intermediates (4a–e) prepared from compounds (3a–e) by chlorosulfonation followed by condensation with corresponding benzothiazole moiety. The synthesized compounds were characterized by IR, ¹H-NMR, ¹³C-NMR spectral data, and elemental analysis, and were evaluated for in vitro antimicrobial activity against certain bacterial and fungal strains using the broth microdilution method as well as antitubercular activity against H₃₇Rv using Lowenstein–Jensen agar method.     

Synthesis, characterization, and antimicrobial screening of some Mannich base sydnone derivatives

The title compounds (5a–j), (6a–j), and (7a–j) were prepared via a four-step procedure using starting material 4-methoxyaniline (1). The structure of all synthesized compounds was confirmed by FT-IR, ¹H NMR, ¹³C NMR, and CHN analysis. The synthesized compounds were tested for their antibacterial and antifungal activity (MIC) in vitro against organisms viz. B. subtilis, S. aureus, E. coli, P. aeruginosa, and C. albicans taking ciprofloxacin, ampicillin, streptomycin, penicillin-G, fluconazole, and nystatin as the standard drugs. Some of the compounds have shown significant activities.     

Synthesis, antitumor activity of 2-amino-4H-benzo[h]chromene derivatives, and structure–activity relationships of the 3- and 4-positions

Several 2-amino-4H-benzo[h]chromenes (3a–i) and (5a–h) were obtained by reaction of 4-chloro-1-naphthol (1) with α-cyanocinnamonitrile (2a–i) or ethyl α-cyanocinnamate derivatives (4a–h), respectively. Structures of these compounds were established on the basis of spectral data. The antitumor activity of the synthesized compounds was investigated in comparison with Vinblastine, Colchicine, and Doxorubicin well-known anticancer drugs, using MTT colorimetric assay. Among them, the compounds 5e, 3c, 5f, b, d, 3d, 5c, a were the most active against MCF-7, 5a against HCT-116 and 5a, 3e, a against HepG-2 as compared with the standard drug Vinblastine, while the compounds 5e, 3c, 5f, b, d, 3d, 5c, a, h, 3i, g, a, e were the most active against MCF-7, 5a, c, e, f, b, 3e, c, g, b, 5d, h, 3d, i, 5g against HCT-116, 5a, 3e, a, 5e, 3c, 5d, c, f, 3b, 5g, 3g, 5h against HepG-2 as compared with the standard drug Colchicine. The structure–activity relationships of the 3- and 4-positions were discussed.     

Synthesis and biological evaluation of some pyrazole derivatives as anti-inflammatory–antibacterial agents

The present article describes the synthesis of two novel series of thiosemicarbazones 3 and thiazolylhydrazinomethylidenepyrazoles 5. All the newly synthesized target compounds (3a–e and 5a–o) were screened for their in vivo anti-inflammatory (AI) activity using carrageenan-induced rat paw edema assay and in vitro antibacterial activity against two Gram-positive and two Gram-negative bacteria. Eight compounds (3b–d, 5b, 5e, 5f, 5i, and 5o) showed consistently excellent AI activity (≥70% inhibition), at 3?and 4?h after the carrageenan injection, comparable to that of standard drug indomethacin (78%) whereas the remaining twelve compounds have shown significant activity with 57–75% inhibition after 3?h and 56–63% inhibition after 4?h. All the tested compounds showed moderate antibacterial properties.     

Microwave-assisted synthesis and antimicrobial screening of new imidazole derivatives bearing 4-thiazolidinone nucleus

A new series of compounds 2-((1-(4-(4-arylidene-2-methyl-5-oxo-4,5-dihydro-1H-imidazol-1-yl)phenyl)ethylidene)hydrazono)thiazolidin-4-ones (4a–o) have been synthesized under conventional and microwave irradiation method. All compounds were characterized by IR, ¹H NMR, ¹³C NMR and mass spectra. Newly synthesized compounds were screened for their antibacterial and antifungal activities on Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus pyogenes, Candida albicans, Aspergillus niger and Aspergillus clavatus by bioassays, namely serial broth dilution. The synthesized compounds showed potent antimicrobial activity against tested microorganisms. Compounds 4h, 4j, 4m and 4n were the most potent amongst tested compounds.     

Synthesis and evaluation of isonicotinoyl hydrazone derivatives as antimycobacterial and anticancer agents

A new series of isonicotinoyl hydrazone derivatives (3a–3o) have been synthesized, characterized and evaluated for in vitro antimycobacterial activity against M. tuberculosis H37Rv and two clinical isolates using tetrazolium microplate assay (TEMA). Some of these compounds showed moderate to good antimycobacterial activity at micro molar concentrations. Among them, 3k and 3m were the most potent analogues with an inhibition concentration at 0.59 and 0.65 μM, respectively, against M. tuberculosis H37Rv compared to parent drug, isoniazid (0.57 μM). Additionally, all the synthesized compounds were subjected to in vitro anticancer activity against human colorectal cancer cell lines (HCT 116). Compounds 3b and 3l displayed antiproliferative activity at inhibitory concentration 3.1 and 0.29 μM, respectively, when compared to standard, 5-fluorouracil (5 μM). These results can be considered as an important start point for the rational design of new leads for antitubercular and anticancer drug discovery.     

Synthesis and antitubercular activity of nucleoside analogs based on L-ascorbic acid and bases

5,6-O-isopropylidene-2,3-di-O-methyl ascorbic acid (2), obtained by reaction of acetone with ascorbic acid (1) followed by methylation with methyl iodide, on 1,8-Diazabicyclo[5.4.0]undec-7-ene-catalyzed elimination of acetone moiety led to the formation of respective 2,3-di-O-methyl didehydro-L-ascorbic acid (4) in good yield. The latter, on methanesulfonylation with methanesulfonyl chloride and subsequent reaction of the crude methanesulfonyloxy derivative with imidazole, benzimidazole, and adenine resulted in the corresponding tetronolactonyl nucleoside analogs 5, 6, and 7. Compound 5 on reaction with benzyl amine led to the N-benzylated teramyl nucleoside analog, while compounds 6 and 7 did not react under similar conditions. All the synthesized compounds were evaluated for their antitubercular activity against M. tuberculosis H₃₇R_a and H₃₇R_v, exhibiting a minimum inhibitory concentration (MIC) of more than12.5 μg/mL.     

Synthesis, antioxidant, and antibacterial studies of phenolic esters and amides of 2-(1-benzofuran-2-yl) quinoline-4-carboxylic acid

A new series of phenolic esters 2(a–j) and amides 3(a–c) of 2-(1-benzofuran-2-yl) quinoline-4-carboxylic acid were synthesized by the reaction of 2-(1-benzofuran-2-yl)-quinoline-4-carboxylic acid (1) with various substituted phenols and secondary amines using ethyl-(N′,N′-dimethylamino)propyl carbodiimide hydrochloride (EDC.HCl) as a coupling agent. The newly synthesized compounds were evaluated for in vitro antioxidant and antibacterial activity. Among all tested compounds 2a, 2c, 2e, and 2h showed good chelating ability with Fe⁺² ions, whereas compounds 2g and 2j exhibited good scavenging activity with DPPH free radicals. Concerning antibacterial activities compounds 2a, 2b, 2c, and 2h were found to be equipotent to ampicillin against Enterococcus sp and Staphylococcus aureus, while compound 2e is found to be as potent as ampicillin against Pantoea Dispersa and Ochrobactrum sp. amide derivatives 3(a–c) were found to be less potent when compared to standard.     

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.