Unexpected formation of 3-chloro-1-hydroxy-2,6-diarylpiperidin-4-ones: Synthesis,antibacterial and antifungal activities

New 3-chloro-1-hydroxy-2,6-diarylpiperidin-4-ones 18–22 were synthesized, characterized by melting point, elemental analysis, MS, FT-IR, one-dimensional NMR (¹H & ¹³C) spectroscopic data and evaluated for their in vitro antibacterial and antifungal activities. All the newly synthesized compounds exerted a wide range of antibacterial activities against the entire tested gram-positive and gram-negative bacterial strains except Escherichia coli. Compounds 21 and 22 exerted strong antifungal activities against Aspergillus flavus, mucor and Microsporum gypsuem. In addition, compound 20 was more potent against Rhizopus.

     

A facile solid-state synthesis and in vitro antimicrobial activities of some 2,6-diarylpiperidin/tetrahydrothiopyran and tetrahydropyran-4-one oximes

Some 2,6-diarylpiperidin/tetrahydrothiopyran/tetrahydropyran-4-one oximes were synthesized in dry media under microwave irradiation and were evaluated for their in vitro antibacterial activity against clinically isolated bacterial strains i.e. S.aureus, beta-H.Streptococcus, E.coli, P.aeruginosa, S.typhii and in vitro antifungal activities against fungal strains i.e. C.albicans, Rhizopus, A.niger and A.flavus. Structure-activity relationships for the synthesized compounds showed that compounds 12 and 15 exerted excellent antibacterial activity against all the tested bacterial strains except 15 against S.aureus and beta-H.streptococcus. Against C.albicans and A.flavus, compound 15 exerted potent antifungal activities while against Rhizopus, compound 16 showed promising activity.     

Synthesis and biological evaluation of novel N-acyl substituted quinolin-2(1H)-one derivatives as potential antimicrobial agents

A series of novel N-acyl substituted quinolin-2(1H)-one derivatives were synthesized and screened in vitro for their antibacterial and antifungal activities by disc diffusion method. All the compounds exhibited moderate to good antimicrobial activities, some of these compounds displayed comparable or better antibacterial or antifungal activities against some tested strains compared to the reference drugs Streptomycin and Fluconazole.     

Synthesis of 13-(substituted benzyl) berberine and berberrubine derivatives as antifungal agents

By introducing various aromatic groups in 13-C of berberine and berberrubine, a series of 13-(substituted benzyl) berberine and berberrubine derivatives were synthesized and examined for antifungal activities against various human pathogenic fungi. The synthesized compounds exhibited more potent antifungal activities than berberine and berberrubine. Among them, 13-(4-isopropyl benzyl) berberine (6e) exerted the most potent antifungal activities against Candida species (MIC=1-8 microg/ml) and a 4-fold stronger activity than 13-(4-isopropyl benzyl) berberrubine (7e) synthesized by pyrolysis of compound 6e.     

Biomimetic synthesis, antimicrobial, antileishmanial and antimalarial activities of euglobals and their analogues

In the present communication, naturally occurring phloroglucinol-monoterpene adducts, euglobals G1-G4 (3b/a and 4a/b) and 16 new analogues (13a/b-18a/b and 19-22) were synthesized by biomimetic approach. These synthetic compounds differ from natural euglobals in the nature of monoterpene and acyl functionality. All of these compounds were evaluated for their antibacterial, antifungal, antileishmanial and antimalarial activities. Analogue 17b possessed good antibacterial activity against methicillin-resistant Staphylococcus aureus, while analogues 19-22 possessed potent antifungal activity against Candida glabrata with IC50s ranging from 1.5 to 2.5 microg/mL. Euglobals along with all synthesized analogues exhibited antileishmanial activity. Amongst these, euglobal G2 (3a), G3 (4a) and analogues 13a and 14a showed potent antileishmanial activity with IC50s ranging from 2.8 to 3.9 microg/mL. Analogue 16a possessed antimalarial activity against chloroquine sensitive D6 clone of Plasmodium falciparum. None of the compounds showed toxicity against mammalian kidney fibroblasts (vero cells) upto the concentration of 4.76 microg/ml.     

Antiprotozoal and antimicrobial activities of O-alkylated and formylated acylphloroglucinols

In the present article, we examined the antileishmanial, antimalarial, antibacterial, and antifungal activities of several newly synthesized O-alkylated phloroglucinol compounds (11-19) which are analogues of the naturally occurring antimalarial compound 1. Analogues 12 and 16 exhibited antileishmanial activity against, Leishmania donovani promastigotes with IC(50)s of 5.3 and 4.2microg/mL, respectively. Naturally occurring monomeric formylated acylphloroglucinol compounds, grandinol (2), jensenone (3), and their analogues (29-37), were also synthesized and evaluated for antileishmanial, antimalarial, antibacterial, and antifungal activities. Amongst these, both grandinol and jensenone showed mild to moderate antibacterial, antifungal, and antileishmanial activities. Jensenone (3) was effective against Candida albicans with an IC(50) of 5.5microg/mL but was ineffective against Cryptococcus neoformans and methicillin-resistant Staphylococcus aureus. Among the analogues, 34 was the most active against C. albicans and C. neoformans with IC(50)s of 2.0 and 2.5microg/mL, respectively, and was fungicidal toward Candida albicans.     

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.     

A facile solid-state synthesis and in vitro antimicrobial activities of some 2,6-diarylpiperidin/tetrahydrothiopyran and tetrahydropyran-4-one oximes

Some 2,6-diarylpiperidin/tetrahydrothiopyran/tetrahydropyran-4-one oximes were synthesized in dry media under microwave irradiation and were evaluated for their in vitro antibacterial activity against clinically isolated bacterial strains i.e. S.aureus, β-H.Streptococcus, E.coli, P.aeruginosa, S.typhii and in vitro antifungal activities against fungal strains i.e. C.albicans, Rhizopus, A.niger and A.flavus. Structure-activity relationships for the synthesized compounds showed that compounds 12 and 15 exerted excellent antibacterial activity against all the tested bacterial strains except 15 against S.aureus and β-H.streptococcus. Against C.albicans and A.flavus, compound 15 exerted potent antifungal activities while against Rhizopus, compound 16 showed promising activity.     

Design, synthesis, and biological evaluation of 1,2,3-trisubstituted-1,4-dihydrobenzo[g]quinoxaline-5,10-diones and related compounds as antifungal and antibacterial agents

A series of (S)-N-(3-chloro-1,4-naphthoquinon-2-yl)-alpha-amino acid ethyl esters 3 and 1,2,3-trisubstituted-1,4-dihydrobenzo[g]quinoxaline-5,10-diones 6-23 were synthesized and evaluated for antifungal and antibacterial activities. The structure-activity relationship of these compounds was studied and the results show that the compounds 3a and 3b exhibited in vitro antifungal activity against Candida albicans, Cryptococcus neoformans, and Sporothrix schenckii whereas compounds 12 and 22 showed in vitro antibacterial activity against Klebsiella pneumoniae and Escherichia coli.     

Synthesis and potent antimicrobial activity of some novel 2-phenyl or methyl-4H-1-benzopyran-4-ones carrying amidinobenzimidazoles

Series of flavones and methyl-4H-1-benzopyran-4-ones carrying mono or diamidinobenzimidazoles at different positions were synthesized and evaluated for antibacterial and antifungal activities against E. coli, S. aureus, MRSA (methicillin-resistant S. aureus), MRSE (methicillin-resistant S. epidermidis), S. faecalis and C. albicans, C. krusei. The results showed that while all diamidines are inactive, the compounds having monoamidinobenzimidazoles at the C-6 position of the 2-phenyl-4H-1-benzopyran-4-one have potent antibacterial activities, particularly, against Gram-positive bacteria. Compounds 23 and 22 exhibited the best inhibitory activity with MIC values of 1.56 microg/ml against S. aureus, MRSA, MRSE and 3.12 microg/ml against C. albicans, respectively.     

Hydrazones of 2-aryl-quinoline-4-carboxylic acid hydrazides: synthesis and preliminary evaluation as antimicrobial agents

A new series of 2-arylquinoline-4-carboxylic acid hydrazide–hydrazones was synthesized using an appropriate synthetic route. All the target compounds were evaluated for their in vitro antimicrobial activity against Staphylococcus aureus as an example for Gram-positive bacteria, Escherichia coli as an example for Gram-negative bacteria, and Candida albicans as a representative of fungi. The minimum inhibitory concentration (MIC) was determined for test compounds as well as for reference standards. Among the compounds tested, compounds having nitro substituents at the arylidene moiety showed the most potent antifungal as well as antibacterial activities against E. coli. Compound 23 displayed an antifungal activity comparable to that of nystatin. However, none of the compounds demonstrated any antibacterial activity against S. aureus. Hydrophobicity of the target compounds correlated weakly with their antibacterial and antifungal activities. The most potent compounds namely, 7, 18, 19, 22, and 23 were assessed for hemolytic toxicity and found to be non-hemolytic up to a concentration of 100 μg/mL. In addition, the most potent compound (23) was evaluated for in vitro cytotoxic activity against various cancer cell lines. This compound was found to display no cytotoxic activity but rather it induces the proliferation rate of Hep-G2 cells.     

Synthesis,antibacterial and antifungal activities of some carbazole derivatives

A series of N-substituted carbazole derivatives were synthesized and evaluated for antibacterial and antifungal activities against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Bacillus proteus, Candida albicans and Aspergillus fumigatus by two fold serial dilution technique. Some of the synthesized compounds displayed comparable or even better antibacterial and antifungal activities than reference drugs fluconazole, chloramphenicol and norfloxacin against tested strains.     

Antimicrobial bioassay of Colchicum luteum Baker

The methanolic extract of the corms of Colchicum luteum Baker (Liliaceae) and its subsequent fractions in different solvent systems were screened for antibacterial and antifungal activities. The crude extract and all the fractions demonstrated moderate to excellent antifungal activities against tested pathogens in antifungal bioassay. Excellent antifungal activity was shown against trichophyton longifusus, up to 75%, and microsporum canis, up to 85%, while the crude extract and subsequent fractions showed mild to moderate activities in an antibacterial bioassay with maximum antibacterial activity 58% against Bacillus subtilis.     

Design, synthesis and evaluation of clinafloxacin triazole hybrids as a new type of antibacterial and antifungal agents

A series of clinafloxacin triazole hybrids as a new type of antibacterial and antifungal agents were synthesized for the first time and screened for their antimicrobial efficacy against four Gram-positive bacteria, four Gram-negative bacteria and two fungi by two fold serial dilution technique. The bioactive assay indicated that most of the target compounds displayed broad antimicrobial spectrum and good antibacterial and antifungal activities with low MIC values ranging from 0.25 to 2μg/mL against all the tested strains which exhibited comparable or even better efficiency in comparison with the reference drugs Chloramphenicol, Clinafloxacin and Fluconazole, respectively. Notably, some synthesized clinafloxacin triazoles showed stronger efficacy against methicillin-resistant Staphylococcus aureus than their parent Clinafloxacin.     

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 antimicrobial activity of some novel nucleoside analogues of adenosine and 1,3-dideazaadenosine

A number of nucleoside analogues have been synthesized and evaluated for their antibacterial and antifungal activities against Staphylococcus aureus, Group D Streptococcus, Pseudomonas aeruginosa, Proteus spp., Salmonella spp., Aspergillus fumigatus, Penicillium marneffei, Candida albicans, Cryptococcus neoformans, and Mucor spp. The compounds 1, 4, and 6 emerged as potent antibacterial agents with MIC values of 0.75, 0.38, and 0.19 microM, respectively, against group D Streptococcus. Further, the results suggest that the molecules 4, 6, and 7 would be potent antifungal agents as they show substantial degree of inhibition toward the growth of pathogenic fungi with MICs of 0.75, 0.38, and 0.38 microM, respectively.     

Structural elucidation and biological significance of 2-hydroxy-1-naphthaldehyde derived sulfonamides and their first row d-transition metal chelates

2-Hydroxy-1-naphthaldehyde derived sulfonamides and their first row d-transition metal chelates [cobalt (II), copper (II), nickel (II) and zinc (II)] have been synthesized and characterized. The nature of bonding and structure of all the compounds have been deduced from elemental analyses, infrared, 1H NMR, 13C NMR, mass spectrometry, electronic spectra, magnetic susceptibility and conductivity measurements. An octahedral geometry has been suggested for all the complexes. The metal complexes were screened for their antibacterial and antifungal activities on different species of pathogenic bacteria and fungi and their biopotency has been discussed. The results of these studies revealed that all compounds showed moderate to significant antibacterial activity against all bacterial strains and good antifungal activity against various fungal strains. In-vitro cytotoxic properties of all the compounds against Artemia salina was also studies by brine shrimp bioassay.     

Synthesis and antimycobacterial properties of N-substituted 6-amino-5-cyanopyrazine-2-carboxamides

A series of fifteen new compounds related to pyrazinamide (PZA) were synthesized, characterized with analytical data and screened for antimycobacterial, antifungal and antibacterial activity. The series consists of 6-chloro-5-cyanopyrazine-2-carboxamide and N-substituted 6-amino-5-cyanopyrazine-2-carboxamides, derived from the previous by nucleophilic substitution with various non-aromatic amines (alkylamines, cycloalkylamines, heterocyclic amines). Some of the compounds exerted antimycobacterial activity against Mycobacterium tuberculosis equal to pyrazinamide (12.5-25 μg/mL). More importantly, 6-chloro-5-cyanopyrazine-2-carboxamide and 5-cyano-6-(heptylamino)pyrazine-2-carboxamide were active against Mycobacterium kansasii and Mycobacterium avium, which are unsusceptible to PZA. Basic structure-activity relationships are presented. Only weak antifungal and no antibacterial activity was detected.     

Synthesis and activities of naphthalimide azoles as a new type of antibacterial and antifungal agents

Naphthalimide-derived azoles as a new type of antimicrobial agents were synthesized and evaluated for their efficiency in vitro against eight bacteria and two fungi by two fold serial dilution technique. Most title compounds exhibited good antimicrobial potency with low MIC values ranging from 1 to 16 μg/mL. Notably, some synthesized compounds displayed comparable or even better antibacterial and antifungal activities against some tested strains than the reference drugs Orbifloxacin, Chloromycin and Fluconazole, respectively.     

Regioselective synthesis and antimicrobial studies of ester linked 1,4-disubstituted 1,2,3-bistriazoles

A series of 1,4-disubstituted 1,2,3-bistriazoles was synthesized via click chemistry by cycloaddition of various bisalkynes with benzyl/2-phenylethyl azide. Synthesized triazoles were characterized by IR, (1)H NMR, (13)C NMR and mass spectral techniques. All the compounds were evaluated for antibacterial/antifungal activities and found to possess moderate to good antimicrobial activities. Further the docking study for the most active compound against DNA Gyrase was also carried out.