Microwave assisted synthesis and antimicrobial evaluation of new fused pyran derivatives bearing 2-morpholinoquinoline nucleus

A new series of fused pyran derivatives 5a-x bearing 2-morpholinoquinoline nucleus has been synthesized under microwave irradiation by a reaction of 2-morpholinoquinoline-3-carbaldehyde 2a-c, malononitrile 3 and compounds 4a-h in presence of NaOH as basic catalyst. All the compounds were screened against three Gram positive bacteria (Streptococcus pneumoniae, Clostridium tetani, Bacillus subtilis), three Gram negative bacteria (Salmonella typhi, Vibrio cholerae, Escherichia coli) and two fungi (Aspergillus fumigatus, Candida albicans) using broth microdilution MIC (Minimum Inhibitory Concentration) method. Of the compounds studied, compounds 5b, 5f, 5k, 5m, 5q, 5s and 5v have found to be most efficient members of the series.     

Antibacterial Diphenyl Ether,Benzophenone and Xanthone Derivatives from Aspergillus flavipes

The extract of the strain Aspergillus flavipes DL‐11 exerted antibacterial activities against six Gram‐positive bacteria. During the following bioassay‐guided separation, ten diphenyl ethers ( 1 – 10 ), two benzophenones ( 11 – 12 ), together with two xanthones ( 13 – 14 ) were isolated. Among them, 4′‐chloroasterric acid ( 1 ) was a new chlorinated diphenyl ether. Their structures were elucidated by extensive spectroscopic data analysis, including IR, HR‐ESI‐MS, NMR experiments, and by comparison with the literature data. All compounds showed moderate to strong antibacterial effects on different Gram‐positive bacteria with MIC values that ranged from 3.13 to 50 μg/mL, but none of the compounds exhibited activity against Gram‐negative bacteria Vibrio parahaemolyticus ATCC17802 (MIC>100 μg/mL). In particular, the MICs of some compounds are at the level of positive control.     

Synthesis and biological evaluation of 2-trifluoromethyl/sulfonamido-5,6-diaryl substituted imidazo[2,1-b]-1,3,4-thiadiazoles: a novel class of cyclooxygenase-2 inhibitors

A series of 2-trifluoromethyl/sulfonamido-5,6-diarylsubstituted imidazo[2,1-b]-1,3,4-thiadiazole derivatives 15a-j have been synthesized by the reaction of 2-amino-5-trifluoromethyl/sulfonamido-1,3,4-thiadiazoles 14a-b and appropriately substituted alpha-bromo-1,2-(p-substituted)diaryl-1-ethanones 13a-h. Structures of these compounds were established by IR, (1)H NMR, (13)C NMR, Mass, and HRMS data. The selected compounds were evaluated for their preliminary in vitro cyclooxygenase inhibitory activity against COX-2 and COX-1enzymes using colorimetric method. The compounds tested showed selective inhibitory activity toward COX-2 (80.6-49.4%) over COX-1 (30.6-8.6), amongst them compounds 15f and 15j showed appreciable COX-2 selective inhibitory activity. These compounds also exhibited significant anti-inflammatory activity (70.09-42.32%), which is comparable to that of celecoxib in the carrageenan-induced rat paw edema method.     

In-vitro antibacterial, antifungal activity of some transition metal complexes of thiosemicarbazone Schiff base (HL) derived from N4-(7'-chloroquinolin-4'-ylamino) thiosemicarbazide

The synthetic, spectroscopic, and biological studies of Cu(II), Ni(II), Zn(II), Co(II), Mn(II), Fe(III) and Cr(III) complexes of N(4)-(7'-chloroquinolin-4'-ylamino)-N(1)-(2-hydroxy-benzylidene)thiosemicarbazone (HL) obtained by the reaction of N(4)-(7'-chloroquinolin-4'-ylamino)thiosemicarbazide with 2-hydroxybenzaldehyde. The structures of the complexes were determined on the basis of the elemental analyses, spectroscopic data (IR, electronic, (1)H and (13)C NMR and Mass spectra) along with magnetic susceptibility measurements, molar conductivity and thermogravimetric analyses. Electrical conductance measurement revealed the non-electrolytic nature of the complexes. The resulting colored products are mononuclear in nature. On the basis of the above studies, only one ligand was suggested to be coordinated to each metal atom by thione sulfur, azomethine nitrogen and phenolic oxygen to form mononuclear complexes in which the thiosemicarbazone behaves as a monobasic tridendate ligand. The ligand and its metal complexes were tested against Gram + ve bacteria (Staphylococcus aureus), Gram - ve bacteria (Escherichia coli), fungi (Candida albicans) and (Fusarium solani). The tested compounds exhibited significant activity.     

Conventional and microwave assisted synthesis of 2-oxo-4-substituted aryl-azetidine derivatives of benzotriazole: a new class of biological compounds

We report herein the synthesis and biological activity of a new kind of azetidinone derivatives of benzotriazole. The reaction was carried out by both conventional and microwave methods. The chemical structures of all the synthesized compounds were deduced according to FTIR, (1)H NMR, (13)C NMR and FAB-mass spectral along with microanalytical data. All the synthesized compounds of series 5a-i were evaluated for their antitubercular activity against Mycobacterium tuberculosis H37RV and antimicrobial activity against some selected microorganism. Unexpectedly, some azetidinone derivatives of benzotriazole displayed better activities.     

Synthesis of acridinyl-thiazolino derivatives and their evaluation for anti-inflammatory, analgesic and kinase inhibition activities

Variety of N-(4-phenyl-3-(2',3',4'(un)substituted phenyl)thiazol-2(3H)-ylidene)-2,4(un)substituted acridin-9-amine (4a-o) and 1-[(2,4-(un)substituted acridin-9-yl)-3-(4-phenyl-3-(2',3',4'(un)substituted phenyl)thiazol-2(3H)-ylidene)]isothiourea (5a-h) derivatives have been synthesized by condensation of 4-phenyl-3-(2',3',4'(un)substituted phenyl)thiazol-2(3H)-imine (3a-g) with 9-chloro-2,4-(un)substituted acridine (1a-c) and 9-isothiocyanato-2,4-(un)substituted acridine (2a-d), respectively. All these compounds were characterized by correct 1H NMR, FT-IR, MS and elemental analyses. These compounds were screened for anti-inflammatory, analgesic and kinase (CDK1, CDK5 and GSK3) inhibition activities. Some compounds exhibited good anti-inflammatory (25-32%) and potent analgesic (50-75%) activities, at 50 mg/kg p.o. A compound, 4o (R1 = H, R2 = OCH3, R3 = CH3, R4 = CH3, R5 = H) exhibited moderate CDK1 (IC50 = 8.5 microM) inhibition activity.     

Synthesis and preliminary biological evaluation of 4,6-disubstituted 3-cyanopyridin-2(1H)-ones, a new class of calcium entry blockers

The preparation of 3-cyano-4,6-diaryl-pyridin-2(1H)-ones 4a-h, calcium entry blockers related to diltiazem, is described starting from 1,3-diaryl-2-propen-1-ones 5. On preliminary pharmacological tests all compounds are active and some of them show calcium antagonistic activity superior or comparable to diltiazem.     

Metal-based biologically active azoles and β-lactams derived from sulfa drugs

Metal complexes of Schiff bases derived from sulfamethoxazole (SMZ) and sulfathiazole (STZ), converted to their β-lactam derivatives have been synthesized and experimentally characterized by elemental analysis, spectral (IR, ¹H NMR, ¹³C NMR, and EI-mass), molar conductance measurements and thermal analysis techniques. The structural and electronic properties of the studied molecules were investigated theoretically by performing density functional theory (DFT) to access reliable results to the experimental values. The spectral and thermal analysis reveals that the Schiff bases act as bidentate ligands via the coordination of azomethine nitrogen to metal ions as well as the proton displacement from the phenolic group through the metal ions; therefore, Cu complexes can attain the square planner arrangement and Zn complexes have a distorted tetrahedral structure. The thermogravimetric (TG/DTG) analyses confirm high stability for all complexes followed by thermal decomposition in different steps. In addition, the antibacterial activities of synthesized compounds have been screened in vitro against various pathogenic bacterial species. Inspection of the results revealed that all newly synthesized complexes individually exhibit varying degrees of inhibitory effects on the growth of the tested bacterial species, therefore, they may be considered as drug candidates for bacterial pathogens. The free Schiff base ligands (1–2) exhibited a broad spectrum antibacterial activity against Gram negative Escherichia coli, Pseudomonas aeruginosa, and Proteus spp., and Gram positive Staphylococcus aureus bacterial strains. The results also indicated that the β-lactam derivatives (3–4) have high antibacterial activities on Gram positive bacteria as well as the metal complexes (5–8), particularly Zn complexes, have a significant activity against all Gram negative bacterial strains. It has been shown that the metal complexes have significantly higher activity than corresponding ligands due to chelation process which reduces the polarity of metal ion by coordinating with ligands.     

Synthesis,molecular modelling and biological evaluation of tetrasubstituted thiazoles towards cholinesterase enzymes and cytotoxicity studies

Alzheimer is a neurodegenerative disease and requires the development of new scaffold to treat it. In this regard, thiazoles derivative are playing their significant role. In the current research paper we have focused our attention for the development of tetrasubstituted thiazole (3a-h) derivatives using domino synthesis by mixing the thiourea as a precursor, with acetophenone in the presence of iodine and tosic acid in DMSO and refluxed for 12–22 h. The structures of the newly synthesized compounds were confirmed by FTIR, ¹H NMR, ¹³C NMR and EIMS analysis. Thiazole derivatives were analyzed for their biological significances against acetyl and butylcholinesterase enzymes and compound 3b and 3d were found more active against these enzyme, respectively. The mode of inhibition was determined for the potent compounds against both the enzymes. Moreover, the molecular docking studies were carried out to explore the interactive behavior of the compounds within the active pocket of enzymes. Furthermore, the derivatives (3a-h) were evaluated for their anticancer potential against HeLa cancer cell lines. Most potent inhibition was observed by compound 3b.     

Microbial transformation of spirolaxine, a bioactive undecaketide fungal metabolite from the basidiomycete Sporotrichum laxum

Incubation of (+)-spirolaxine (= (3R)-5-hydroxy-7-methoxy-3-{5-[(2R,5R,7R)-2-methyl-1,6-dioxaspiro[4.5]dec-7-yl]pentyl}-2-benzofuran-1(3H)-one; 1a) with Bacillus megaterium afforded two new mono- and one new dihydroxylated metabolite(s), all OH groups being introduced on the non-activated six-membered ring. In contrast, exposure of 1a to Cunninghamella echinulata gave rise to hydroxylation on the five-membered ring of the parent structure. The structures and absolute configurations of the new products 1b-e were deduced on the basis of MS and NMR data. The metabolite 1b was investigated, in comparison to 1a, for its cytotoxicity (sulforhodamin-B test) and for its antiproliferative activity towards bovine microvascular endothelial cells (BMEC).     

Synthesis and Antimicrobial Evaluation of Novel Chiral 2‐Amino‐4,5,6,7‐tetrahydrothieno[2,3‐c]pyridine Derivatives

New N‐substituted‐2‐amino‐4,5,6,7‐tetrahydrothieno[2,3‐c]pyridine derivatives were synthesized employing a convenient one‐pot three‐component method and their structures were characterized by ¹H‐NMR and single crystal X‐ray diffraction analysis. All the synthesized compounds were in vitro screened for antimicrobial activity against Gram‐positive (Sarcina lutea) and Gram‐negative bacteria (Escherichia coli). In this work, we introduced a chiral residue on the tetrahydropyridine nitrogen, the hitherto the less investigated position on this pharmacophore in order to explore the effect. The antibacterial results showed that the synthesized compounds were active only against Gram‐positive bacteria and the (R)‐enantiomers displayed a greater antimicrobial potency than their (S)‐counterparts. The structure–activity relationship here investigated may provide some interesting clues for future development of tetrahydrothienopyridine derivatives with higher antimicrobial activity.     

In-vitro antibacterial,antifungal activity of some transition metal complexes of thiosemicarbazone Schiff base (HL) derived from N4-(7′-chloroquinolin-4′-ylamino) thiosemicarbazide

The synthetic, spectroscopic, and biological studies of Cu(II), Ni(II), Zn(II), Co(II), Mn(II), Fe(III) and Cr(III) complexes of N⁴-(7′-chloroquinoline-4′-ylamino)-N¹-(2-hydroxy-benzylidene)thiosemicarbazone (HL) obtained by the reaction of N⁴-(7′-chloroquinolin-4′-ylamino)thiosemicarbazide with 2-hydroxybenzaldehyde. The structures of the complexes were determined on the basis of the elemental analyses, spectroscopic data (IR, electronic, ¹H and ¹³C NMR and Mass spectra) along with magnetic susceptibility measurements, molar conductivity and thermogravimetric analyses. Electrical conductance measurement revealed the non-electrolytic nature of the complexes. The resulting colored products are mononuclear in nature. On the basis of the above studies, only one ligand was suggested to be coordinated to each metal atom by thione sulfur, azomethine nitrogen and phenolic oxygen to form mononuclear complexes in which the thiosemicarbazone behaves as a monobasic tridendate ligand. The ligand and its metal complexes were tested against Gram + ve bacteria (Staphylococcus aureus), Gram ? ve bacteria (Escherichia coli), fungi (Candida albicans) and (Fusarium solani). The tested compounds exhibited significant activity.     

Sulfonamide-1,2,4-triazole derivatives as antifungal and antibacterial agents: synthesis, biological evaluation, lipophilicity, and conformational studies

A series of 10 new 5-[2-(substituted sulfamoyl)-4,5-dimethoxy-benzyl]-4aryl-s-triazole-3-thiones were synthesized and evaluated for in vitro antifungal and antibacterial activity. All compounds tested showed significant antifungal activity against all the micromycetes, compared to the commercial fungicide bifonazole. Differences in their activity depend on the substitution of different reactive groups. More specifically, best antifungal activity among synthetic analogues was shown with N-dimethylsulfamoyl group. All the compounds tested against bacteria showed the same activity as the commercial agent streptomycin, except for Enterobacter cloacce and Salmonella species. Chloramphenicol showed lower bactericidal effect than the synthetic compounds. Furthermore, it is apparent that different compounds reacted in different ways against bacteria. Gram (-) bacteria seem to be more sensitive to these compounds than Gram (+) species. An effort was made to correlate the above-mentioned differences in activity with lipophilicity studies. Furthermore, molecular modeling was used to obtain the main conformational features of this class of molecules for future structure-activity relationship studies.     

Synthesis and evaluation of uterine relaxant activity for a novel series of substituted p-hydroxyphenylethanolamines

Novel racemic 1-(4-hydroxyphenyl)-2-[3-(substituted phenoxy)-2-hydroxy-1-propyl]aminopropan-1-ol hydrochlorides (9a-h) were synthesized by condensing racemic 1-(p-hydroxyphenyl)-2-aminopropan-1-ol hydrochloride (6) with substituted aryloxymethyloxiranes (8a-h) in DMF in presence of anhydrous potassium carbonate and then reacting with dry hydrogen chloride gas. They were evaluated for uterine relaxant activity in vitro on isolated rat uterus and in vivo in pregnant rats. Their cAMP releasing potential was studied using rat uterus tissue homogenates by cAMP [3H] assay and cardiac stimulant potential was evaluated in dog. All compounds exhibited potent uterine relaxant activity in vitro and produced a significant delay in the onset of labour in pregnant rats; their cAMP releasing potential was higher than isoxsuprine hydrochloride except for 9b and 9c. Finally insignificant cardiac stimulant potential was noted for these compounds when compared to isoxsuprine hydrochloride.     

Simple, fast and efficient synthesis of β-keto esters from the esters of heteroaryl compounds, its antimicrobial study and cytotoxicity towards various cancer cell lines

A series of β-keto esters were synthesized from heteroaryl esters and ethyl acetate using LiHMDS as base at -50 to -30 °C. The increase in yields of cross condensed product were observed and the percentage of self condensed product was reduced drastically by applying the suitable base (LiHMDS), solvent and the minimum amount of ethyl acetate. All these β-keto esters were characterized using (1)H NMR, (13)C NMR and mass spectral data. A plausible mechanism is also depicted to prove the formation of trans-esterified products. All the synthesized compounds were subjected to test for their cytotoxicity towards various cancer cell lines and also tested for their antimicrobial activity towards various bacterial and fungal strains and some of them were found to have promising activity.     

Antimicrobial, spectral, magnetic and thermal studies of Cu(II), Ni(II), Co(II), UO(2)(VI) and Fe(III) complexes of the Schiff base derived from oxalylhydrazide

The Schiff base ligand, oxalic bis[(2-hydroxybenzylidene)hydrazide], H(2)L, and its Cu(II), Ni(II), Co(II), UO(2)(VI) and Fe(III) complexes were prepared and tested as antibacterial agents. The Schiff base acts as a dibasic tetra- or hexadentate ligand with metal cations in molar ratio 1:1 or 2:1 (M:L) to yield either mono- or binuclear complexes, respectively. The ligand and its metal complexes were characterized by elemental analyses, IR, (1)H NMR, Mass, and UV-Visible spectra and the magnetic moments and electrical conductance of the complexes were also determined. For binuclear complexes, the magnetic moments are quite low compared to the calculated value for two metal ions complexes and this shows antiferromagnetic interactions between the two adjacent metal ions. The ligand and its metal complexes were tested against a Gram + ve bacteria (Staphylococcus aureus), a Gram -ve bacteria (Escherichia coli), and a fungi (Candida albicans). The tested compounds exhibited high antibacterial activities.     

Synthesis and pharmacological activities of some mononuclear Ru(II) complexes

A series of mononuclear Ru(II) complexes of the type [Ru(M)2(U)]2+, where M = 2,2'-bipyridine/1,10-phenanthroline and U = tpl (Ru1), 4-Cl-tpl (Ru2), 4-CH3-tpl (Ru3), 4-CH3O-tpl (Ru4), and 4-NO2-tpl (Ru5), -pai (Ru6), where tpl = thiopicolinanilide and pai = 2-phenyl-azo-imidazole, have been prepared and characterized by IR, UV-Vis, 1H NMR, 13C-NMR, FAB-Mass spectrophotometer, and elemental analysis. The complexes display metal-ligand charge transfer (MLCT) transitions in the visible region. The title complexes were subjected to in vivo anticancer activity tests against a transplantable murine tumor cell line, Ehrlich's ascitic carcinoma (EAC) and in vitro antibacterial activity against Gram positive and Gram negative microorganisms. Ru1-Ru6 were found to increase the life span of the tumor hosts by 19-52%, and decreased tumor volume and viable ascitic cell count. The results of the present study clearly demonstrated the tumor inhibitory activity of the ruthenium chelates against transplantable murine tumor cell line. The treatment with ruthenium complexes could be secondary to tumor regression or due to the action of the compounds itself. The significant antibacterial activity was observed for Ru1-Ru4 against microorganisms like Vibrio cholera 865, Staphylococcus aureus 6571, and Shigella flexneri as compared to that of standard drug chloramphenical. Ru5 showed moderate activity against S. aureus 8530. However, all the complexes fail to show significant antibacterial activity against V. cholera 14033 and Shigella sonnai.     

Highly effective, water-soluble, hemocompatible 1,3-propylene oxide-based antimicrobials: poly[(3,3-quaternary/PEG)-copolyoxetanes

This study focuses on the solution antimicrobial effectiveness of a novel class of copolyoxetanes with quaternary ammonium and PEG-like side chains. A precursor P[(BBOx-m)(ME2Ox)] copolyoxetane was prepared by cationic ring-opening copolymerization of 3-((4-bromobutoxy)methyl)-3-methyloxetane (BBOx) and 3-((2-(2-methoxyethoxy)ethoxy)methyl)-3-methyloxetane (ME2Ox) to give random copolymers with 14-100 (m) mol % BBOx. Reaction of P[(BBOx-m)(ME2Ox)] with dodecyl dimethylamine gave the corresponding quaternary P[(C12-m)(ME2Ox)] polycation salts, designated C12-m, as viscous liquids in 100% yield. BBOx/ME2Ox and C12/ME2Ox ratios were obtained by (1)H NMR spectroscopy. C12-m molecular weights (M(n), 3.5-21.9 kDa) were obtained from (1)H NMR end group analysis. DSC studies up to 150 °C showed only thermal transitions between -69 and -34 °C assigned to T(g) values. Antibacterial activity for the C12-m copolyoxetanes was tested by determining minimum inhibitory concentrations (MICs) against Gram(+) Staphylococcus aureus and Gram(-) Escherichia coli and Pseudomonas aeruginosa . MIC decreased with increasing C12 mol percent, reaching a minimum in the range C12-43 to C12-60. Overall, the antimicrobial with consistently low MICs for the three tested pathogenic bacteria was C12-43: (bacteria, MIC, μg/mL) E. coli (6), S. aureus (5), and P. aeruginosa (33). For C12-43, minimum biocidal concentration (MBC) to reach 99.99% kill in 24 h required 1.5× MIC for S. aureus and 2× MIC for E. coli and P. aeruginosa . At 5× MIC against a challenge of 10(8) cfu/mL, C12-43 kills ≥99% S. aureus , E. coli , and P. aeruginosa within 1 h. C12-m copolyoxetane cytotoxicity toward human red blood cells was low, indicating good prospects for biocompatibility. The tunability of C12-m copolyoxetane compositions, effective antimicrobial behavior against Gram(+) and Gram(-) bacteria, and promising biocompatibility offer opportunities for further modification and potential applications as therapeutic agents.     

Synthesis,molecular docking studies,and antimicrobial evaluation of new structurally diverse ureas

A series of new urea derivatives (3a-p) have been synthesized from readily available isocyanates and amines in good to high yields. All synthesized compounds were fully characterized using ¹H NMR, ¹³C NMR, IR, and mass spectrometry. Additionally, the structure of the compound (3n) was confirmed by single-crystal X-ray diffraction. Furthermore, all compounds were evaluated for antimicrobial activity against five bacteria and two fungi. Last but not the least, molecular docking studies with Candida albicans dihydropteroate synthetase were performed and the results are presented herein.     

Biocidal activity of some Mannich base cationic derivatives

A novel series of cationic surfactants was prepared based on Mannich base (produced from the condensation of piperidine and/or morpholine as secondary amine and paraformaldehyde in the presence of 8-hydroxyquinoline). The chemical structures of the synthesized cationic surfactants were confirmed using elemental analyses, FTIR spectroscopy and 1H NMR. Surface activities of the prepared surfactants were measured including: surface tension (gamma), critical micelle concentration (CMC), effectiveness (pi(CMC)), efficiency (Pc20), maximum surface excess (Gamma(max)), minimum surface area (A(min)), interfacial tension (gamma(IT)), emulsification power and foaming power at 25 degrees C. The structural influences on their surface activities and adsorption free energy were discussed. The synthesized cationic surfactants were evaluated for their biocidal activity towards Gram +ve bacteria (Staph. Cocu., Bacillus), Gram -ve bacteria (Salmonella, E. coli), fungi (A. terrus., A. flav.) and yeast (Candida) at 1.0, 2.5 and 5.0mg/mL, respectively. The target compounds showed good inhibition towards Gram +ve bacteria, Gram -ve bacteria and yeast. Meanwhile, excellent fungicidal results were obtained against the various types of fungi under investigation.