Synthesis and antifungal activity of 1H-indole-4,7-diones

1H-Indole-4,7-diones were synthesized and tested for in vitro antifungal activity against fungi. The synthesized 1H-indole-4,7-diones generally showed good antifungal activity against Candida krusei, Cryptococcus neoformans, and Aspergillus niger. The results suggest that 1H-indole-4,7-diones would be potent antifungal agents.     

Synthesis and antifungal activity of 1H-pyrrolo[3,2-g]quinoline-4,9-diones and 4,9-dioxo-4,9-dihydro-1H-benzo[f]indoles

1H-Pyrrolo[3,2-g]quinoline-4,9-diones and 4,9-dioxo-4,9-dihydro-1H-benzo[f]indoles were synthesized and tested for in vitro antifungal activity against fungi. Among them tested, many compounds showed good antifungal activity. The results suggest that 1H-pyrrolo[3,2-g]quinoline-4,9-diones and 4,9-dioxo-4,9-dihydro-1H-benzo[f]indoles would be potent antifungal agents.     

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.     

Design, synthesis and evaluation of 2-phenyl-1H-benzo[d]imidazole-4,7-diones as vascular smooth muscle cell proliferation inhibitors

A series of 2-phenyl-1H-benzo[d]imidazole-4,7-diones were synthesized and tested for their inhibitory activity on the PDGF-stimulated proliferation of rat aortic vascular smooth muscle cells. Among the tested compounds, 6-arylthio-5-chloro-2-phenyl-1H-benzo[d]imidazole-4,7-diones exhibited an potent antiproliferative activity.     

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.     

Synthesis and antifungal activity of 1-thia-4b-aza-cyclopenta[b]fluorene-4,10-diones

1-Thia-4b-aza-cyclopenta[b]fluorene-4,10-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 1-thia-4b-aza-cyclopenta[b]fluorene-4,10-diones would be antifungal agents.     

Synthesis and biological evaluation of 5-arylamino-1H-benzo[d]imidazole-4,7-diones as inhibitor of endothelial cell proliferation

5-Arylamino-1H-benzo[d]imidazole-4,7-diones were synthesized and tested for their inhibitory activities on the proliferation of human umbilical vein endothelial cells (HUVECs) and the smooth muscle cells (SMCs). Among them, several 1H-benzo[d]imidazole-4,7-diones exhibited the selective antiproliferative activity on the HUVECs. Further mechanistic study revealed that the inhibitory effect of one representative 1H-benzo[d]imidazole-4,7-dione 2b on HUVEC proliferation was mediated by the activation of p38 signaling pathway in the HUVECs.     

Synthesis and antifungal activity of 5-arylamino-4,7-dioxobenzo[b]thiophenes

5-Arylamino-4,7-dioxobenzo[b]thiophenes 3-6 were synthesized and tested for in vitro antifungal activity against Candida and Aspergillus species. 5-Arylamino-6-chloro-2-(methoxycarbonyl)-4,7-dioxobenzo[b]thiophenes 5 showed, in general, more potent antifungal activity against Candida species than the other 4,7-dioxobenzo[b]thiophenes 3, 4 and 6. The results suggest that 5-arylamino-4,7-dioxobenzo[b]thiophenes would be potent antifungal agents.     

Transformations of six isomers of dimethylbenzothiophene by three Pseudomonas strains

Dimethylbenzothiophenes are among the sulfur heterocycles in petroleum that are known to be degraded by microbial activity. Six of the 15 possible isomers of dimethylbenzothiophene were synthesized and used in biotransformation studies with three Pseudomonas isolates that oxidize a variety of condensed thiophenes including methylbenzothiophenes and methyldibenzothiophenes. The isomers of dimethylbenzothiophene were chosen to have a variety of substitution patterns: both methyl groups on the thiophene ring (the 2,3- isomer); a methyl group on each of the rings (the 2,7-, 3,5- and 3,7-isomers); and both methyl groups on the benzene ring (the 4,6- and 4,7- isomers). Each isolate was grown on 1-methylnaphthalene or glucose in the presence of one of the dimethylbenzothiophenes and culture extracts were analyzed to identify nearly 30 sulfur-containing metabolites in total. Sulfoxides and sulfones were commonly found metabolites in culture extracts from the 2,3-, 2,7- and 3,7-isomers, whereas 2,3-diones, 3(2H)-ones and 2(3H)-ones were formed from the 4,6- and 4,7-isomers. High-molecular-weight products, some of which were tentatively identified as tetramethylbenzo[b]naphtho[1,2-d]thiophenes, were detected in the extracts of cultures incubated with 4,6- or 4,7-dimethylbenzothiophene. The methyl groups of all of the isomers, except 4,6-, were oxidized to give hydroxymethyl-methylbenzothiophenes and methylbenzothiophene-carboxylic acids, and these were the only products detected from the oxidation of 3,5-dimethylbenzothiophene.     

Synthesis and biological evaluation of benzimidazole-4,7-diones that inhibit vascular smooth muscle cell proliferation

A series of 6-arylamino-5-chloro-benzimidazole-4,7-diones were synthesized and tested for their inhibitory activity on the rat aortic smooth muscle cell (RAoSMC) proliferation. Among them, 6-arylamino-5-chloro-2-methyl-benzimidazole-4,7-diones exhibited potent antiproliferative activity. Benzimidazole-4,7-dione 2c activated SAPK/JNK signaling pathway in the RAoSMCs.     

Synthesis and antifungal activity of 6,7-bis(arylthio)-quinazoline-5,8-diones and furo[2,3-f]quinazolin-5-ols

6,7-Bis(arylthio)-quinazoline-5,8-dione and furo[2,3-f]quinazolin-5-ol derivatives were synthesized and tested for in vitro antifungal activity against Candida, Aspergillus species, and Cryptococcus neoformans. Among them tested, many of furo[2,3-f]quinazolin-5-ols and 6,7-bis(arylthio)-quinazoline-5,8-diones showed good antifungal activity. The compounds completely inhibited the growth of all against Candida and Aspergillus species tested at the MIC level of 12.5μg/mL. The results suggest that furo[2,3-f]quinazolin-5-ols and 6,7-bis(arylthio)-quinazoline-5,8-diones would be promising antifungal agents.     

Synthesis and antifungal activity of furo[2,3-f]quinolin-5-ols

Furo[2,3-f]quinolin-5-ol derivatives were synthesized and tested for in vitro antifungal activity against Candida,Aspergillus species, and Cryptococcus neoformans. Among them tested, many furo[2,3-f]quinolin-5-ols showed good antifungal activity. The results suggest that furo[2,3-f]quinolin-5-ols would be promising antifungal agents.     

Studies on synthesis of novel pyrido[2,3-d]pyrimidine derivatives,evaluation of their antimicrobial activity and molecular docking

A series of novel pyrido[2,3-d]pyrimidine derivatives 6 were prepared starting from 2-amino-3-cyano-4-trifluoromethyl-6-phenyl pyridine 3 via Grignard’s reaction, cyclization followed by coupling with aliphatic and cyclic amines. All the compounds 6 were screened for antibacterial, minimum bactericidal concentration (MBC), biofilm inhibition activity as well as antifungal and minimum fungicidal concentration (MFC) activities. Among the screened compounds, the compounds 6e, 6f, and 6m which showed exhibiting promising activity have been identified. The results reveal that the compound pyrido[2,3-d]pyrimidine derivative 6e altered the sterol profile which may exert its antifungal activity through inhibition of ergosterol biosynthesis and could be an ideal candidate for antifungal therapy. The molecular docking results also validated the antifungal results.     

Synthesis and antifungal activity of 6-arylamino-phthalazine-5,8-diones and 6,7-bis(arylthio)-phthalazine-5,8-diones

6-Arylamino-phthalazine-5,8-diones and 6,7-bis(arylthio)-phthalazine-5,8-diones were synthesized and tested for in vitro antifungal activity against two pathogenic strains of fungi. Among those tested, many compounds showed good antifungal activity. The results suggest that phthalazine-5,8-diones would be potent antifungal agents.     

2-Substituted-1-(2-morpholinoethyl)-1H-naphtho[2,3-d]imidazole-4,9-diones: Design,synthesis and antiproliferative activity

Thirty-six of novel compounds 2-substituted-1-(2-morpholinoethyl)-1H-naphtho[2,3-d]imidazole-4,9-diones, bearing a N-(2-morpholinoethyl) group and a 2-substituted imidazole segment on a naphthoquinone skeleton, were designed, synthesized and tested as anticancer agents. Cytotoxicity was evaluated in vitro against three human cancer cell lines: human breast carcinoma cell line (MCF-7), human cervical carcinoma cell line (Hela), and human lung carcinoma cell line (A549); and one normal cell line: mouse fibroblast cell line (L929). Among them, the compound 2-(3-chloro-4-methoxyphenyl)-1-(2-morpholinoethyl)-1H-naphtho[2,3-d]imidazole-4,9-dione showed good antiproliferative activity against MCF-7, Hela and A549 (IC₅₀ values are equal to 10.6?μM, 8.3?μM and 4.3?μM respectively) and low cytotoxicity to L929 (IC₅₀ value is equal to 67.3?μM).     

Synthesis and antimicrobial activity of novel fluorine containing 4-(substituted-2-hydroxybenzoyl)-1H-pyrazoles and pyrazolyl benzo[d]oxazoles

A series of fluorine containing 4-(substituted-2-hydroxybenzoyl) pyrazoles and pyrazolyl benzo[d]oxazoles were synthesized and evaluated for their antibacterial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Bacillus subtilis and antifungal activity against Candida albicans. The antibacterial activities were expressed as the minimum inhibitory concentration (MIC₅₀) in μg/ml. The compounds 1-(3,4-difluorophenyl)-4-(5-fluoro-2-hydroxybenzoyl)-1H-pyrazole (4b), oxime derivatives such as 1-(3,4-difluorophenyl)-1H-pyrazol-4-yl)(2-hydroxy-4-methylphenyl)methanone oxime (5b) and (5-chloro-2-hydroxyphenyl)(1-(3,4-difluorophenyl)-1H-pyrazol-4-yl)methanone oxime (5e) exhibited promising activities against tested bacterial strains. Except compound 1-(3,4-difluorophenyl)-4-(2-hydroxybenzoyl)-1H-pyrazole (4d), none of the other compounds showed promising antifungal activity.     

Synthesis and antifungal activity of noble 5-arylamino- and 6-arylthio-4,7-dioxobenzoselenazoles

5-Arylamino- and 6-arylthio-4,7-dioxobenzoselenazoles 4 and 5 were synthesized and tested for in vitro antifungal activity against Candida and Aspergillus species. 5-Arylamino-4,7-dioxobenzoselenazoles 4 showed, in general, more potent antifungal activity than 6-arylthio-4,7-dioxobenzoselenazoles 5. The results suggest that 5-arylamino-4,7-dioxobenzoselenazoles 4 would be potent antifungal agents.     

Synthesis and antibacterial activity study of a novel class of cationic anthraquinone analogs

Reported previously by our group, one-pot cycloaddition using naphthoquinone, sodium azide and alkyl halides can lead to the formation of both 1-alkyl-1H- and 2-alkyl-2H-naphtho[2,3-d]triazole-4,9-diones. Herein, the effect of leaving group and additive in dictating the selectivity between the formation of 1-alkyl-1H- and 2-alkyl-2H-naphtho[2,3-d]triazole-4,9-diones has been further investigated. In the process of investigating the factors that control the selectivity and the biological activity associated with these two compounds, a novel class of antibacterial cationic anthraquinone analogs has been developed. Although these compounds are structurally similar, different antibacterial profiles are noted. One lead compound, 4e manifests high potency (MIC < 1 ??g/mL) and selectivity against Gram positive (G+) pathogens including methicillin-resistant Staphylococcus aureus (MRSA) while exerting only modest activity against Gram negative (G−) bacteria. Other lead compounds (4f and 4g) exhibit broad antibacterial activity including MRSA and vancomycin-resistant Enterococcus faecalis (VRE) that is comparable to other commercially available cationic antiseptic chemicals. This unique difference in antibacterial profile may pave the way for the development of new therapeutic agents.     

Reaction of naphthoquinones with substituted nitromethanes. Facile synthesis and antifungal activity of naphtho[2,3-d]isoxazole-4,9-diones

We report here a simple entry into naphtho[2,3-d]isoxazole-4,9-dione system containing a EWG in position 3 using the readily available 2,3-dichloro-1,4-naphthoquinone and nitromethyl derivatives in the presence of base. Antifungal activity of synthesised naphthoquinones was evaluated against ATCC and PYCC reference strains of Candida. The results suggest that the naphtho[2,3-d]isoxazole-4,9-dione scaffold has the potential to be developed into novel and safe therapeutic antifungal agents.     

Natural products as sources of new fungicides (V): Design and synthesis of acetophenone derivatives against phytopathogenic fungi in vitro and in vivo

A series of acetophenone derivatives (10a–10i, 11, 12a–12g, 13a–13g, 14a–14d and 15a–15l) were designed, synthesized and evaluated for antifungal activities in vitro and in vivo. The antifungal activities of 53 compounds were tested against several plant pathogens, and their structure–activity relationship was summarized. Compounds 10a–10f displayed better antifungal effects than two reference fungicides. Interestingly, the most potent compound 10d exhibited antifungal properties against Cytospora sp., Botrytis cinerea, Magnaporthe grisea, with IC₅₀ values of 6.0–22.6?µg/mL, especially Cytospora sp. (IC₅₀?=?6.0?µg/mL). In the in vivo antifungal assays, 10d displayed the significant protective efficacy of 55.3% to Botrytis cinerea and 73.1% to Cytospora sp. The findings indicated that 10d may act as a potential pesticide lead compound that merits further investigation.