Synthesis and biological evaluation of novel (L)-alpha-amino acid methyl ester, heteroalkyl, and aryl substituted 1,4-naphthoquinone derivatives as antifungal and antibacterial agents

A series of (S)-N-(1,4-naphthoquinon-2-yl)-alpha-amino acid methyl esters 3-9, 2-N,N-dialkylamino-1,4-naphthoquinones 10-11 and 2-hydroxy-3-(2'-mercaptoimidazolyl)-1,4-naphthoquinones and their cyclic analogs 12-15 were synthesized and evaluated for antifungal and antibacterial activities. The structure-activity relationships of these compounds were studied and the results show that the compounds 9b and 13c exhibited in vitro antifungal activity against Candida albicans, Cryptococcus neoformans, and Sporothrix schenckii, whereas compound 6a showed in vitro antibacterial activity against Streptococcus faecalis, K. pneumoniae, Escherichia coli, and Staphylococcus aureus.     

Synthesis of (1,4)-naphthoquinono-[3,2-c]-1H-pyrazoles and their (1,4)-naphthohydroquinone derivatives as antifungal, antibacterial, and anticancer agents

A series of (1,4)-naphthoquinono [3,2-c]-1H-pyrazoles and their (1,4)-naphthohydroquinone derivatives 2-7 were synthesized and evaluated for antifungal, antibacterial, and anticancer activities. The structure-activity relationship of these compounds was studied and the results show that the compound 2b exhibited in vitro antifungal activity against Candida albicans and Cryptococcus neoformans, and also possessed antibacterial profile against Klebsiella pneumoniae and Escherichia coli whereas 1c showed anticancer activity against Walker 256 Carcinosarcoma in rats.     

Naphtho[2,3-b][1,4]-thiazine-5,10-diones and 3-substituted-1,4-dioxo-1,4-dihydronaphthalen-2-yl-thioalkanoate derivatives: synthesis and biological evaluation as potential antibacterial and antifungal agents

A series of 3-substituted-1,4-dioxo-1,4-dihydronaphthalen-2-yl-thio-alkanoate derivatives 3-21 and naphtho[2,3-b][1,4]-thiazine-5,10-diones 24 were synthesized and evaluated for their antibacterial and antifungal activities. The structure-activity relationships of these compounds were studied and the results show that the compound 24a exhibited better antibacterial activity than Gentamycin in vitro against Staphylococcus aureus. In addition 24a also imparted marked antifungal activity in vitro against Cryptococcus neoformans, Sporothrix schenckii, and Trichophyton mentagraphytes when compared with Fluconazole. Compounds 15, 18, 19, and 21 also exhibited significant antibacterial activity in vitro against S. aureus.     

Synthesis and evaluation of novel 1,4-naphthoquinone derivatives as antiviral, antifungal and anticancer agents

The synthesis and evaluation of some 2-substituted-1,4-naphthoquinones 2, S-(1,4-naphthoquinon-2-yl)-mercaptoalkanoic acid amides 4, related benzoquinone and naphthoquinone derivatives 6-9 and 2,3-disubstituted 1,4-naphthoquinones 10-11 were carried out. The antifungal, antibacterial, antiviral and anticancer activities were determined by using the standard assay. The results show that compounds 2b and 10a showed in vitro antiviral activity against Influenza-A Virus and Herpes Simplex Virus and possess pronounced antifungal profile whereas 4a showed anticancer activities against Lymphoid Leukaemia P 388.     

Synthesis and antifungal evaluation of 6-hydroxy-1H-carbazole-1,4(9H)-diones

6-Hydroxy-1H-carbazole-1,4(9H)-diones were synthesized and tested for in vitro antifungal activity against two pathogenic strains of fungi. Among them tested, many compounds showed good antifungal activity. The results suggest that 6-hydroxy-1H-carbazole-1,4(9H)-diones would be potent antifungal agents.     

Synthesis and antifungal evaluation of pyrido[1,2-a]indole-1,4-diones and benzo[f]pyrido[1,2-a]indole-6,11-diones

Pyrido[1,2-a]indole-1,4-diones and benzo[f]pyrido[1,2-a]indole-6,11-diones were synthesized and tested for in vitro antifungal activity against two pathogenic strains of fungi. Among them tested, many compounds showed good antifungal activity. The results suggest that pyrido[1,2-a]indole-1,4-diones and benzo[f]pyrido[1,2-a]indole-6,11-diones would be potent antifungal agents.     

A convenient 'one-pot' synthesis and in vitro microbiological evaluation of novel 2,7-diaryl-[1,4] -diazepan-5-ones

A convenient method for the 'one-pot' synthesis of novel target molecule 2,7-diaryl-[1,4]-diazepan-5-ones from the respective 2,6-diaryl-piperidin-4-ones was catalyzed by NaHSO4.Al2O3 heterogeneous catalyst in dry media under microwave irradiation in solvent-free conditions. Moreover, the catalyst could be recovered and re-used up to 4 times after washing with ethyl acetate. They were evaluated for potential antibacterial activity against Staphylococcus aureus, beta-Haemolytic streptococcus, Vibreo cholerae, Salmonella typhii, Escherichia coli, Klebsiella pneumonia, Pseudomonas and antifungal activity against Aspergillus flavus, Aspergillus fumigatus, Mucor, Candida albicans and Rhizopus. Structure-Activity Relationship (SAR) led to the conclusion that, of all the compounds 25-32 tested, compound 30 exerted strong in vitro antibacterial activity against S. aureus, S. typhii, and Pseudomonas and all the compounds 25-32 were less active against E. coli, whereas all the compounds 25-32 displayed potent in vitro antifungal activity against all the fungal strains used, except compound 30, which was more effectual against Mucor.     

Micelles catalyzed chemoselective synthesis 'in water' and biological evaluation of oxygen containing hetero-1,4-naphthoquinones as potential antifungal agents

Various oxygen containing 1,4-naphthoquinone derivatives have been synthesized chemoselectively by an economical, viable green methodology approach using water as solvent with or without surfactants such as Triton X-100, SDS, LD (laundry detergent), and TBAB, a phase transfer catalyst and evaluated for their in vitro antifungal and antibacterial activity. The antifungal profile of 3, 4a, 4b, and 6 indicated that compounds 3a, 3b, 4b, 6a, and 6c have potent antifungal activity compared to clinically prevalent antifungal drugs Fluconazole and Amphotericin-B against Sporothrix schenckii, Trichophyton mentagraphytes, and Candida parapsilosis and compound 3b has been found to be a lead antifungal agent for further study.     

Antimicrobial activity studies on some piperidine and pyrrolidine substituted halogenobenzene derivatives

The in vitro antibacterial and antifungal activities of the compounds synthesised from some 1,2,3,5-tetrahalogeno benzenes in presence of sodium piperidide and sodium pyrrolidide (2,6-dipiperidino-1,4-dihalogenobenzenes; 2,6-dipyrrolidino-1,4-dibromobenzene; 2,4,6-tripyrrolidino chlorobenzene; and 1,3-dipyrrolidino benzene) were investigated. The in vitro antimicrobial activities were screened against the standard strains: Staphylococcus aureus ATCC 25923 and Bacillus subtilis ATCC 6633 as Gram positive, Yersinia enterocolitica ATCC 1501, Escherichia coli ATCC 11230 and Klebsiella pneumoniae as Gram negative, and Candida albicans as yeast-like fungus. Compounds (3, 5, 6, 7) inhibited the growth of all the test strains at MIC values of 32-512 microg/ml. None of the four compounds (1, 2,4,8) studied showed antimicrobial activity against any of the test strains within the MIC range 0.25-512 micro/ml.     

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 antifungal activity of 6-hydroxycinnolines

6-Hydroxycinnolines 2 and cyclohexa-2,5-diene-1,4-dione derivatives 6 were synthesized and tested for in vitro antifungal activity against Candida and Aspergillus species. 6-Hydroxycinnolines 2 showed, in general, more potent antifungal activity against Candida species than the other cyclohexa-2,5-diene-1,4-diones. The results suggest that 6-hydroxycinnolines would be potent antifungal agents.     

Design,synthesis, biological activities and DFT calculation of novel 1,2,4-triazole Schiff base derivatives

Series of 1,2,4-triazole Schiff bases (2a-2d, 2f-2h and 3a-3h) have been designed and synthesized. The structure of title compounds was confirmed on the basis of their spectral data and elemental analysis. All the target compounds were screened for their in vitro antifungal activity and antibacterial activity. Two of the tested compounds (2a and 2b) exhibited significant antifungal activity against most fungi, especially compound 2a showed better antifungal activity than triadimefon. Meanwhile, the antibacterial activity assay also indicated compound 2a exhibited excellent antibacterial activities comparable to chloramphenicol. The SAR manifested no substitution at position 5 of the triazole ring caused an increase in activity, and 3-phenoxy phenyl group introduced in 1,2,4-triazole scaffold can enhance the antibacterial activity. The DFT calculation indicated triazole ring, S atom and benzene ring in both of the 2a and 3a make a major contribution to the activity.     

Antifungal activity of rhodium, iridium, and ruthenium tripodal phosphine complexes

Twenty-eight rhodium, iridium or ruthenium complexes were evaluated for their in vitro antifungal activities against Candida albicans and Candida tropicalis. Fourteen compounds showed an antifungal activity against C. albicans and C. tropicalis with a range of the minimum inhibitor concentrations (MICs) between 16 and 250 micrograms/mL.     

Synthesis and evaluation of novel 3a,9a-dihydro-1-ethoxycarbonyl-1-cyclopenteno[5,4-b]benzopyran-4-ones as antifungal agents

An efficient synthesis of novel antifungal 3a,9a-dihydro-1-ethoxycarbonyl-1-cyclopenteno[5,4-b]benzopyran-4-ones (10a-j) through 1,3-dipolar cycloaddition of all carbon 1,3-dipole (7) with substituted 3-formylchromones (8a-j) has been developed. The synthesized compounds were characterized spectroscopically and evaluated in vitro for antifungal activity against various strains. Some of the compounds 10b, 10d and 10i exhibit significant inhibitory potential against Aspergillus niger, Saccahromyces cerevisiae and Candida albicans.     

Antimicrobial activity of ZnII, CdII, and HgII complexes of 1,2-bis-[2-(5-R)-1H-benzimidazolyl]-1,2-ethanediols and 1,4-bis-[2-(5-R)-1H-benzimidazolyl]-1,2,3,4-butanetetraols

1,2-Bis-[2-(5-H/Me/Cl/NO2)-1H-benzimidazolyl]-1,2-ethanediols (L1-L4), 1,4-bis-[2-(5-H/Me/Cl)-1H-benzimidazolyl]-1,2,3,4-butanetetraols (L5-L7) and their complexes with ZnCl2, CdCl2 and HgCl2 were synthesized and antibacterial activity of the compounds was tested toward Staphylococcus aureus, S. epidermidis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhi, Shigella flexneri, Proteus mirabilis and antifungal activity against Candida albicans. HgII complexes have a considerably higher antimicrobial activity against all microorganisms. Some HgII complexes show higher antifungal activity than clotrimazole toward C. albicans. Zn2(L3)Cl4, Zn2(L4)Cl4, and Cd(L3)Cl2 were moderately effective against S. aureus and S. epidermidis; Cd(L4)Cl2 exhibited a weak activity only against S. epidermidis.     

Synthesis of organometallic-based biologically active compounds: In vitro antibacterial, antifungal and cytotoxic properties of some sulfonamide incorporated ferrocences

Sulfonamides incorporated ferrocene (SIF) have been synthesized by the condensation reaction of sulfonamides (sulfanilamide, sulfathiazole or sulfamethaxazole) with 1,1'-diacetylferrocene. The synthesized compounds (SIF(1)-SIF(4)) have been characterized by their physical, spectral and analytical properties and have been screened for their in vitro antibacterial properties against pathogenic bacterial strains e.g., Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis Staphylococcus aureus and Salmonella typhi and for antifungal activity against Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glaberata using Agar-well diffusion method. Most of the compounds showed good antibacterial activity whereas, all the compounds exhibited significant antifungal activity. Brine shrimp bioassay was also carried out for in vitro cytotoxic properties against Artemia salina.     

Antimicrobial activity of 1,2-bis-[2-(5-R)-1H-benzimidazolyl]-1,2-ethanediols, 1,4-bis-[2-(5-R)-1H-benzimidazolyl]-1,2,3,4-butanetetraols and their FeIII, CuII, and AgI complexes

1,2-Bis-[2-(5-H/Me/Cl/NO2)-1H-benzimidazolyl]-1,2-ethanediols (L1-L4), 1,4-Bis-[2-(5-H/Me/Cl)-1H-benzimidazolyl]-1,2,3,4-butanetetraols (L5-L7) and their complexes with FeCl3, CuCl2, and AgNO3 were synthesized; antibacterial activity of the compounds was determined toward Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhi, Shigella flexneri, Proteus mirabilis, and antifungal activity against Candida albicans. The AgI complexes have considerable activity toward the microorganisms. Some AgI complexes show higher activity toward S. epidermidis than AgNO3 and cefuroxime. Cu(L3)Cl2 and Fe(L3)Cl3 show an antifungal effect on C. albicans but L3 itself has no activity.     

Synthesis and evaluation of demethoxyviridin derivatives as potential antimicrobials

The in vitro antibacterial and antifungal activities of demethoxyviridin and some synthetic analogues were evaluated by the agar diffusion method. The minimum inhibitory concentrations (MIC) of the active compounds were also determined by the agar dilution method. Demethoxyviridin (1) showed moderate antibacterial activity against most of the strains tested. 1alpha-Hydroxydemethoxyviridin (3) showed antibacterial activity and the most potent in vitro antifungal activity with MIC of 20 microg/ml (0.062 mM) against Aspergillus niger, A. fumigatus, A. flavus, A. parasiticus, Fusarium solani, F. graminarum, Geotrichum candidum whereas 5'-methylfuro-(4',3',2'-4,5,6)androst-5-ene-3,17-dione (7) exhibited very weak antifungal activity against Candida albicans only.     

2-Hydroxyphenacyl azoles and related azolium derivatives as antifungal agents

2-Hydroxyphenacyl azole and 2-hydroxyphenacyl azolium compounds have been described as a new class of azole antifungals. Most target compounds showed significant in vitro antifungal activities against tested fungi (Candida albicans, Saccharomyces cerevisiae, Aspergillus niger, and Microsporum gypseum) with low MICs values included in the range of 0.25-32 microg/mL comparable to reference drug fluconazole. The most active compounds were also assessed for their cytotoxicity using MTT colorimetric assay on normal mouse fibroblast (NIH/3T3) cells. The results of antifungal activity and toxicity tests indicated that these compounds display antifungal activity at non-cytotoxic concentrations.