Synthesis and biological evaluation of 1-(3-chloro-2-oxo-4-phenylazetidin-1-yl)-3-(2-oxo-2-(10H-phenothiazin-10-yl)ethyl)urea derivatives

A new series of eleven novel 1-(3-chloro-2-oxo-4-phenylazetidin-1yl)-3-(2-oxo-2-(10H-phenothiazin-10-yl)ethyl)urea derivatives were synthesized by cyclocondensation of various Schiff bases of phenothiazine with chloroacetyl chloride in the presence of triethylamine. Various Schiff bases of phenothiazine were synthesized by condensation of 4-(2-oxo-2-(10H-phenothiazin-10-yl)ethyl semicarbazide with various aryl aldehydes. The synthesized compounds were characterized by IR, MASS and ¹H NMR spectral data and evaluated for in vitro antimicrobial, antitubercular, antioxidant and anticancer activities by disc diffusion method, MIC method, REMA, DPPH, FRAP and MTT assay method, respectively. All synthesized compounds showed moderate-to-significant anti-bacterial and anti-fungal activity and compound 4d, 4g, 4h and 4k showed good antioxidant activity with EC₅₀ value of 55, 57, 56 and 47 μg/ml tested by DPPH method. The compounds 4j at a concentration of 10 μg/ml showed inhibition against the growth of Mycobacterium tuberculosis and 4f showed significant activity against human cervical cancer cell line with IC₅₀ values of 18.26 μM.     

Synthesis and antibacterial evaluation of 3,3′-diindolylmethane derivatives

Various 3,3′-diindolylmethane (DIM) derivatives were synthesized and the antibacterial activity of these compounds were tested against ten bacterial strains and their minimum inhibitory concentration (MIC) values were determined. The MIC values of derivatives 3a–d and 5a–e were ranging from 125 to 500 μg/mL. Among these derivatives, 2-(di(1H-indol-3-yl)methyl)phenol (5a) and 3-((1H-indol-3-yl)(pyridin-3-yl)methyl)-1H-indole (5d) exhibited potent activity, showing MIC values 6.5–62.5 μg/mL against Gram positive and Gram negative bacteria. Hemolytic assay of these active DIM derivatives did not show considerable toxic effect on the normal human erythrocytes.     

In vitro microbiological evaluation of 1,1'-(5,5'-(1,4-phenylene)bis(3-aryl-1H-pyrazole-5,1-(4H,5H)-diyl))diethanones, novel bisacetylated pyrazoles

An efficient, one-pot synthesis was developed for 3-aminoalkylated indoles by three-component coupling reaction of aldehydes, N-methylanilines, and indoles using AgOTf as a catalyst. A series of twenty 3-aminoalkylated indoles was evaluated for their antibacterial activities against both Gram negative and Gram positive bacteria. Compounds 4b and 4r showed good antibacterial activity against both Gram positive and Gram negative strains. However, inversing the property of substituent (from 4r to 4q) resulted in the significant fall in the magnitude of antibacterial activity against Escherichia coli.     

Computational POM evaluation of experimental in vitro Trypanosoma cruzi and Mycobacterium tuberculosis inhibition of heterocyclic-2-carboxylic acid (3-cyano-1,4-di-noxidequinoxalin-2-yl)amide derivatives

A computation model has been developed for the rational design of bioactive pharmacophore sites as anti-Mycobacterium tuberculosis and anti-Trypanosoma cruzi (TC) candidates. The 40 compounds 1–40 analyzed have been previously screened for their antitubercular and antitrypanosomal activity. The highest anti-TC activity is obtained for compounds 8 and 18 which exhibited low IC₅₀ values (9.2 and 10.8 μM), almost equal to clinical drug, nifurtimox (7.7 μM; 100 % Inhib.). This could be attributed to the existence of two synergic (O ^δ?–N ^δ?) and (O ^δ?–O ^δ?) antitrypanosomal pharmacophore sites. In contrast to compounds 8 and 18 which contain electro-attractor groups (R¹, R² = F), analog compounds 1 and 13 with electro-donor or only hydrogen (R¹, R² = CH₃, H) show best antibacterial activity (MIC = 0.977 and 1.190 μg/mL) very close to antitubercular activity of Rifampicin (MIC = 0.125 μg/mL). This could be attributed to the existence of (O ^δ?–NH ^δ+) antibacterial pharmacophore site.     

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, anticancer, anti-HIV-1, and antimicrobial activity of some tricyclic triazino and triazolo[4,3-e]purine derivatives

In an effort to etablish new candidates with improved antineoplastic, anti-HIV-1 and antimicrobial activities, the synthesis of some new triazino and triazolo[4,3-e]purine derivatives is described: 6,8-dimethyl-1,4-dihydro-1,2,4-triazino[4,3-e]purine-7,9(6H, 8H)-diones 3–6; 5,7,9-trimethyl-1,2,4-triazolo[4,3-e]purine-6,8(5H, 7H, 9H)-diones 11–13, together with the synthesis of the 8-substituted purine derivative: 8-(3,5-diamino-1H-pyrazol-4-yl)diazenyl-1,3-dimethyl-1H-purine-2,6(3H, 7H)-dione 7. The prepared compounds were tested for their in vitro anticancer, anti-HIV and antimicrobial activities. The results of the in vitro anticancer screening revealed that compound 3 exhibited considerable activity against melanoma MALME-3?M, non-small lung cancer HOP-92 and breast cancer T-47D (GI₅₀ values of 25.2, 31.8, and 32.9?μM, respectively). The anti-HIV-1 results indicated that compounds 7 and 13c displayed moderate activity (maximum % cell protection 30.52 and 35.54 at 2?×?10^?4 M, respectively). The in vitro antimicrobial data showed that compound 12 was the most active against P. aeruginosa, it was equipotent to ampicillin (MIC?<?100?μg/ml). While compound 11d was the most active against P.?vulgaris, it was as active as ampicillin (MIC?<?50?μg/ml). In addition, compounds 12 and 13c were the most active against S. aureus (MIC?<50 and <25?μg/ml, respectively). On the other hand, the tested compounds devoid of antifungal activity except 6b and 11c which showed weak activity against A.?niger.     

Synthesis and antimicrobial activity of 5-((3-aryl-1-phenyl-1H-pyrazol-4-yl)methylene)thiazolidine-2,4-diones

A series of 5-((3-aryl-1-phenyl-1H-pyrazol-4-yl)methylene)thiazolidine-2,4-diones was synthesized by Knoevenagel condensation of various 3-aryl-1-phenyl-1H-pyrazole-4-carbaldehydes (1a–h) with thiazolidine-2,4-dione (2) in ethanol in the presence of piperidine. All compounds were screened for their in vitro antibacterial (Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa and Escherichia coli) activity and compared with the commercially available antibiotic, ciprofloxacin. All compounds showed good activity against gram-positive bacteria, however, none of the compounds were found to be effective against gram-negative bacteria. Compound 3g was found to be most potent member among all the compounds showing MIC of 16?μg/ml against S. aureus and 32?μg/ml against B. subtilis. All the synthesized compounds were also tested for their in vitro antifungal (Aspergillus niger and A. flavus) activity and compared with commercially available fluconazole. They showed excellent antifungal activity. Compounds 3b, 3e, 3f and 3g were active against both fungi showing more than 60% inhibition. Compound 3e was found to be superior to the reference drug.     

Synthesis and antimicrobial activity of novel derivatives of Biginelli pyrimidines

A series of novel Biginelli pyrimidines was prepared and evaluated for antimicrobial activity. Weak inhibitory activity (MIC?=?128?μg/ml) was observed from 3b and 8b, against S. aureus and P. aeruginosa, respectively. Moderate antifungal agents: 4c, 4d, 4e with MIC?=?32?μg/ml, 3d, 7b, and 8b with MIC?=?64?μg/ml against C. albicans were determined. 4c, 4d, 4e, and 7b proved to be moderate antifungals against A. niger with MIC?=?64?μg/ml.     

Synthesis and evaluation of substituted 5-(3-chloro-2-oxo-4-phenylazetidin-1-ylamino)pyrimidine-2,4,6(1H,3H,5H)-triones against pentylenetetrazole-induced convulsant in mice

This study was designed to synthesis of substituted 5-(3-chloro-2-oxo-4-phenylazetidin-1-ylamino)pyrimidine-2,4,6(1H,3H,5H)-triones followed by evaluation against pentylenetetrazole-(PTZ) induced convulsant in mice. The titled compounds were confirmed by IR and ¹H-NMR spectral techniques. Pre-treatment of compound 4c showed significant anticonvulsant activity at 40?mg/kg which was comparable to that of PTZ and sodium valproate pre-treated groups. The results show the importance of barbituric acid derivative (i.e., compound 4c (R?=?p-OH, m-OCH₃) for this anti-convulsant activity. It may be due to its anti-oxidative and neuroprotective potential. Therefore, compound 4c emerged as the most active molecules in the management of convulsive disorder.     

Synthesis, characterization, and SAR studies of new (1H-indol-3-yl)alkyl-3-(1H-indol-3-yl)propanamide derivatives as possible antimicrobial and antitubercular agents

In this article, we report herein the SAR studies of a series of (1H-indol-3-yl)alkyl-3-(1H-indol-3-yl)propanamide 10(a–j), 11(a–j). The synthesized compounds were evaluated for their preliminary in vitro antibacterial, antifungal activity and were screened for antitubercular activity against Mycobacterium tuberculosis H37Rv strain. The synthesized compounds displayed interesting antimicrobial activity.     

Discovery of 2-(4-cyano-3-trifluoromethylphenyl amino)-4-(4-quinazolinyloxy)-6-piperazinyl(piperidinyl)-s-triazines as potential antibacterial agents

A series of 2-(4-cyano-3-trifluoromethylphenyl amino)-4-(4-quinazolinyloxy)-6-piperazinyl(piperidinyl)-s-triazines have been synthesized in this study by a simple and efficient synthetic protocol. The synthetic route to final piperazinyl s-triazines involved two nucleophilic substitution reactions of 4-amino-2-trifluoromethyl-benzonitrile and 4-hydroxyquinazoline with 2,4,6-trichloro-1,3,5-triazine resulting in 2,4-disubstituted-6-chloro-1,3,5-triazine derivative to introduce the piperazinyl or piperidinyl functionality. The structures of the compounds were elucidated with the aid of IR, ¹H NMR, ¹³C NMR, ¹⁹F NMR spectroscopy, and elemental analysis. The antimicrobial activity of the compounds was tested against eight bacteria (Staphylococcus aureus MTCC 96, Bacillus cereus MTCC 619, Escherichia coli MTCC 739, Pseudomonas aeruginosa MTCC 741, Klebsiella pneumoniae MTCC 109, Salmonella typhi MTCC 733, Proteus vulgaris MTCC 1771, Shigella Flexneria MTCC 1457) and four fungi (Aspergillus niger MTCC 282, Aspergillus fumigatus MTCC 343, Aspergillus clavatus MTCC 1323, and Candida albicans MTCC 183). The title compounds were also investigated for their antituberculosis activity against MTB H37 R_V strain using BACTEC MGIT and L. J. agar dilution method. The bioassay results showed that compounds 5d, 5n, 5p, 5s, and 5t demonstrated 99% inhibition at the MIC of 6.25?μg/ml, equivalent to standard drug pyrazinamide.     

Synthesis, in vitro antimicrobial, antiproliferative, and QSAR studies of N-(substituted phenyl)-2/4-(1H-indol-3-ylazo)-benzamides

In this study, N-(substituted phenyl)-2/4-(1H-indol-3-ylazo)-benzamides (1–26) were synthesized and screened for their in vitro antibacterial (Gram positive; S. aureus, B. subtilis and Gram negative; E. coli) and antifungal (C. albicans and A. niger) activities. The antimicrobial activity results indicated that compound, 4-(1H-indol-3-ylazo)-N-(4-nitro-phenyl)-benzamide (12, pMIC_am = 1.61) was the most potent. In general, it was found that the synthesized compounds were bacteriostatic/fungistatic in action except fungicidal for A. niger. The synthesized compounds were also evaluated for their antiproliferative activity against human colon cancer (HCT116), murine leukemia (P388), and breast cancer (MCF7) cell lines. The antiproliferative study results demonstrated 4-(1H-indol-3-ylazo)-N-p-tolyl-benzamide (2, IC₅₀ = 0.0003 μM/mL) and 4-(1H-indol-3-ylazo)-N-p-tolyl-benzamide (21, 0.0003 μM/mL) as lead compounds for the development of novel antiproliferative agents. The QSAR studies indicated the importance of topological parameters, Kier’s alpha second-order shape indice (κα₂) and Wiener index (W) in describing the antimicrobial activity of the synthesized compounds.     

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.     

Synthesis and biological evaluation of fatty imidazolines

A series of eight fatty imidazolines were synthesized under microwave-assisted conditions using different fatty acids namely octyl, decyl, dodecyl, tetradecyl and octadecyl, mixed fatty acids prepared from Sterculia foetida (containing cyclopropene-rich fatty acids), coconut (containing medium-chain-rich fatty acids), palm (containing saturated-rich fatty acids) and sunflower (containing unsaturated-rich fatty acids). Coconut, sunflower and non-edible oil S. foetida-based imidazolines were synthesized for the first time. The fatty imidazolines were evaluated for anti-fungal activity and found to be good to excellent (MIC, 4.68–18.75 μg ml^?1) against the tested Candida strains as compared with fluconazole (MIC, 16–64 μg ml^?1) as standard. The fatty imidazolines also exhibited excellent to moderate anti-bacterial activity (MIC, 4.68–75 μg ml^?1) against Staphylococcus aureus MTCC 96, S. aureus MLS 16 MTCC 2940 and Pseudomonas aeruginosa MTCC 2453 as compared with neomycin (MIC, 18.75 μg ml^?1) as standard. The cytotoxic evaluation of the imidazolines against different cancer cell lines such as HeLa (Human Cervical Cancer Cell line), A549 (Human Alveolar Adenocarcinoma Cell line), MDA-MB-231& MCF7 (Human Breast Adenocarcinoma Cell line) and Neuro2a (Mouse neuroblastoma cell line) showed excellent cytotoxicity for dodecyl (3b), tetradecyl (3c), octadecyl (3d) and coconut (3f)-based imidazolines. Sunflower-based imidazoline (3g) exhibited good anti-cancer activity towards A549, Neuro2a and palm-based imidazoline (3h) towards HeLa, A549 and MCF-7 cell lines.     

Synthesis of novel 3-(5-sulfanyl-1,3,4-oxadiazol-2-yl)-2H-chromen-2-one condensed s-triazinyl piperazines and piperidines as antimicrobial agents

Synthesis and antimicrobial activity of a new series of 3-(5-sulfanyl-1,3,4-oxadiazol-2-yl)-2H-chromen-2-ones based on various substituted piperazines and piperidines incorporating a 1,3,5-triazine moiety are reported in this article. 3-{5-[(4,6-dichloro-1,3,5-triazin-2-yl)sulfanyl]-1,3,4-oxadiazol-2-yl}-2H-chromen-2-one 3 was obtained by the reaction of 2,4,6-trichloro-1,3,5-triazine 1 with 3-(5-sulfanyl-1,3,4-oxadiazol-2-yl)-2H-chromen-2-one 2 which was obtained by following the method reported in the literature. Intermediate 3 was then condensed with 8-hydroxyquinoline 4 to form 3-(5-{[4-chloro-6-(quinolin-4-yloxy)-1,3,5-triazin-2-yl]sulfanyl}-1,3,4-oxadiazol-2-yl)-2H-chromen-2-one 5. This was further treated with various substituted piperazines and piperidines to obtain the title compounds 7a–u, which were then subjected to determine their in vitro biological efficacy against bacterial and fungal strains as two Gram-positive bacteria (S. aureus, B. cereus), six Gram-negative bacteria (E. coli, P. aeruginosa, K. pneumoniae, S. typhi, P. vulgaris, and S. flexneria) and two fungal species (A. niger, and C. albicans) with an intent to develop novel class of antimicrobial agents. The results indicate that some of the novel s-triazines have noteworthy activity in MIC (μg/ml) and zone of inhibition (mm) indicating potential leads for further drug discovery study. All the final compounds were structurally elucidated on the basis of IR, ¹H NMR, ¹³C NMR, ¹⁹F NMR spectroscopy, and elemental analysis.     

Synthesis and in vitro antibacterial activity of schiff bases of N-substituted isatins as effective scaffolds

Novel Schiff bases of N-substituted isatin, 1–13, were synthesized starting from isatin and N-(4-amino-2-methylphenyl)-4-chlorophthalimide and their structures were confirmed by spectral and elemental analyses. All new compounds were tested for their in vitro antibacterial activity against a range of Gram +ve bacterial strains, like Bacillus subtilis (NCIM-2156), Staphylococcus aureus (NCIM-2079) and Staphylococcus epidermis (NCIM-2493) and Gram ?ve bacterial strains, like Pseudomonas aeruginosa (NCIM-2036), Escherichia coli (NCIM-2065) and Proteus vulgaris (NCIM-2027) following broth dilution method as recommended by the National Committee for clinical laboratory standards using ciprofloxacin as reference. Determination of minimum inhibitory concentration (MIC) and zone of inhibition showed that the molecules were more active against Gram ?ve bacteria than Gram +ve bacteria. The compounds showed promising antibacterial properties with MIC ranging between 10 and 30 μg/mL.     

Synthesis and biological evaluation of some N4-substituted 5-nitroisatin-3-thiosemicarbazones

A series of 5-nitroisatin-3-thiosemicarbazones 2a–2l was synthesised and evaluated for selected biological activities. The brine shrimp lethality bioassay was carried out to study their in vitro cytotoxicity potential and besides, their antifungal, phytotoxic and urease inhibitory effects were also investigated. Only compound 2j proved to be active in the brine shrimp assay exhibiting LD₅₀ value 1.16?×?10^?3?M. Compounds 2a and 2d displayed moderate antifungal activity (50 and 40%, respectively) against M. canis. Similarly, compound 2l exhibited moderate activity (40%) against the fungal strain, A. flavus. In phytotoxicity assay, all the synthesised compounds including the reference point 2m showed weak to moderate (20–60%) activity at the highest tested concentrations (1,000?μg and 500?μg/ml, respectively). In urease inhibition assay, compounds 2a, 2i and 2k proved to be potent inhibitors demonstrating pronounced inhibition with IC₅₀ values 0.440, 0.901 and 27.880?μM, respectively. These compounds may act as leads for further studies.     

Synthesis of novel 2-alkyl-4-substituted-amino-pyrazolo[3,4-d]pyrimidines as new leads for anti-bacterial and anti-cancer activity

Treatment of 6-alkyl-1-phenyl-4-chloro-(1H)-pyrazolo[3,4-d]pyrimidines, with different amines afforded a series of compounds whose identity and purity were confirmed by spectral and analytical means. The compounds were tested for antibacterial activity against four organisms viz. Staphylococcus aureus (Gram positive), S. epidermidis (Gram positive), Bacillus subtilis (Gram positive), Escherichia coli (Gram negative) using amoxicillin as standard control. Compounds 4d, 6b, 6c have shown best antibacterial activity in the series. The antiproliferative activity was tested against human skin cancer cell line G361. The compounds 3d, 4d, 5b, 5d, 5e, 6c, 7a were found to be the best of the series and showed the activity at micromolar concentration.     

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.