Design and synthesis of novel triazole derivatives containing γ-lactam as potential antifungal agents

A series of novel triazole derivatives containing γ-lactam were designed and synthesized, and their structures were confirmed by ~1H NMR,~(13)CNMR and HRMS. The in vitro antifungal activities of the target compounds were evaluated. The results showed that all of the compounds exhibited stronger activity against the six clinically important fungi tested than fluconazole. 3D and 3E showed comparative activity against the fungi tested except for Candida glabrata and Aspergillus fumigatus as voriconazole. In addition,the docking model for 2A and CYP51 was investigated.     

Design and synthesis of novel triazole antifungal derivatives based on the active site of fungal lanosterol 14a-demethylase （CYP51）

A series of 1-(1H-1,2,4-triazole-1-y1)-2-(2,4-difluorophenyl)-3-(N-isoproyl-N-substituted-amino)-2-propanols have been designed and synthesized on the basis of the active site of lanosterol 14a-demethylase(CYP51).Their structures were confirmed by MS and ~1H NMR.In vitro antifungal activities of these synthesized compounds were evaluated against eight human pathogenic fungi.The results showed that all title compounds exhibited activity against fungi tested to some extent.Compounds 3c,3d,7a,7b and 7c exhi...     

Synthesis and in vitro Study of Novel Methylenebis(phenyl- 1,5-benzothiazepine)s and Methylenebis(benzofuryl-1,5- benzothiazepine)s as Antimicrobial Agents

A series of methylenebis(phenyl-1,5-benzothiazepine)s 4 and methylenebis(benzofuryl-1,5-benzothiazepine)s 5 were prepared by the reaction of methylene-bis-chalcones 3 with 2-aminothiophenol for 4 and followed by the condensation with chloroacetone for 5. The structures of the synthesized compounds have been confirmed by their IR, 1H NMR, 13C NMR, MS and elemental analyses. All the synthesized compounds were tested for their antimicrobial activity against Gram-positive, Gram-negative bacteria and fungi. To elucidate the essential structural requirements for the antimicrobial activity, the preliminary structure-activity relationship has been described. Among the compounds tested, the dimeric compounds 4f, 4g, 5f and 5g were found to be most active against Bacillus subtilis, Bacillus sphaericus, Staphylococcus aureus, Klebsiella aerogenes and Chromobacterium violaceum. Similarly these dimeric compounds showed potent antifungal activity against Candida albicans, Aspergillus fumigatus, Trichophyton rubrum, and Trichophyton mentagrophytes. It is interesting to note that the dimeric compounds with substituents of heterocyclic ring at the 4th position of benzothiazepine system displayed notable antibacterial activity equal to that of streptomycin and penicillin. Further, the activity of all the dimeric compounds was compared with that of their monomeric compounds, and it is interesting to note that almost all the dimeric compounds showed enhanced activity than their monomeric compounds.     

Silica‐gel‐supported Phosphorus Pentoxide:a Simple and Efficient Solid‐supported Reagent for Esterification of Long‐ Chain Carboxylic Acids and Their Antimicrobial Screening

A silica-gel-supported heterogeneous phosphorus pentoxide reagent has been developed for the esterification of various long-chain carboxylic acids with aromatic alcohols. The reactions occurred under relatively mild conditions and afforded the desired products in good yields. All the compounds 3a—3x were screened for antibacterial and antifungal activity, which showed good activity against Gram positive and Gram negative bacteria and also good results against almost all fungal strains. The structures of the synthesized compounds were elucidated by IR, ¹H NMR, ¹³C NMR, mass spectroscopic techniques and elemental analysis.     

Synthesis, Structural Investigations and Biological Screening of Diorganotin(IV) Complexes Derived from 5,5-Diethyl Sodium Barbital

Some biologically important tin(IV) complexes derived from 5,5-diethyl sodium barbital have been synthesized and characterized through various analytical and spectroscopic techniques such as IR, 1H-, 13C-NMR and 119mSn mssbauer. On the basis of these spectroscopic techniques, octahedral geometry has been assigned to all the novel compounds. These complexes, soluble in DMSO and DMF, were screened against a wide range of microorganisms. The results proved that the diphenyltin(IV) and dibutyltin(IV) complexes exhibit excellent activity against all types of microorganisms, while the rest of the compounds show significant activity that can be used during the biological study.     

Synthesis,Structural Investigations and Biological Screening of Diorganotin（Ⅳ） Complexes Derived from 5,5-Diethyl Sodium Barbital

Some biologically important tin（Ⅳ） complexes derived from 5,5-diethyl sodium barbital have been synthesized and characterized through various analytical and spectroscopic techniques such as IR, ^1H-, ^13C-NMR and ^119mSn mossbauer. On the basis of these spectroscopic techniques, octahedral geometry has been assigned to all the novel compounds. These complexes, soluble in DMSO and DMF, were screened against a wide range of microorganisms. The results proved that the diphenyltin（Ⅳ） and dibutyltin（Ⅳ） complexes exhibit excellent activity against all types of microorganisms, while the rest of the compounds show significant activity that can be used during the biological study.     

Synthesis and fungicidal activity study of novel daphneolone analogs with 2,6-dimethylmorpholine

A series of novel daphneolone analogs was designed and synthesized on the basis of natural product 1,5-diphenyl-2-penten-1-one(I) from Stellera chamaejasme L. as lead compound, whereby 2,6-dimethylmorpholine moiety was introduced to replace 1-phenyl group. Their structures were confirmed by IR,1H NMR, and HRMS(ESI) or elemental analysis,13 C NMR for some representative compounds. The two isomers of target compounds were separated and identified by NOESY technique and chemical method.All of the synthesized compounds have been evaluated for anti-plant pathogenic fungi activities. The results showed that some compounds exhibited moderate to good antifungal activities against tested fungi at the concentration of 50 mg/L. Among them, compound 7d, with a 4-bromine-substituted phenyl group and cis-2,6-dimethylmorpholine moiety, displayed best activity with an EC50 of 23.87 mmol/L against Valsa mali, superior to lead compound I. In addition, preliminary structure–activity relationship analysis indicated that, between two isomers of target compounds, the antifungal activities of the isomer with cis-2,6-dimethylmorpholine were better than the trans-isomer.     

Synthesis and Antileishmanial Activities of Some New Azasterols

A series of novel azasterols 8a―8h and 10a―10c were synthesized from the key intermediate 6 by acylation and deprotection.Compound 6 was obtained through a series of reactions including Wittig reaction,etherification,ene reaction,oxidation,oximation and reduction.Structures of the synthesized compounds were confirmed by IR,MS and 1H NMR.Furthermore,all of these compounds were screened for in vitro antiparasitic activity against L.donovani.Among them,compounds 8h,10a and 10b showed a fair inhibition of leishmania promastigotes growth at 25 μg/mL,with potencies close to that of the reference drug,amphotericin B.The results provide a starting point for the development of novel drugs to treat leishmaniasis.     

Environmentally Benign Synthesis of 2-Pyrazolines and Cyclohexenones Incorporating Naphthalene Moiety and Their Antimicrobial Evaluation

We reported the environmental benign synthesis of chalcones,2-pyrazolines and cyclohexanones under microwave irradiation.Chalcones were obtained by the condensation of each of 2-hydroxyacetophenone derivatives with a-naphthaldehyde under microwave irradiation.The condensation reactions of each of synthesized chalcones with phenyl hydrazine under microwave irradiation in the presence of dry acetic acid as a cyclizing agent gave 2-pyrazolines.Also,the new cyclohexenone derivatives,valuable intermediates to synthesize fused heterocycles,have been prepared by the cyclocondensation of each of hydroxychalcones with ethyl acetoacetate.The structures of the synthesized compounds were elucidated by infrared（IR） spectrometry,nuclear magnetic resonance（NMR）,mass spectrometry（MS） and elmental analysis.The results indicate that unlike classical heating,microwave irradiation results in higher yields with shorter and cleaner reactions.The synthesized compounds were screened for antimicrobial activity against Staphylococcus aureus,Escherichia coli,Candida Albicans and Aspergillus niger.We clarified the effects of different substituents in the tested compounds on the obtaind antibacterial activities and antifungal activities.     

Synthesis of some heteroaryl pyrazole derivatives and their biological activities

In order to search for novel fungicides with high activity, a series of heteroaryl pyrazoles were synthesized from 5-pyra-zole formhydrazide. The structures of all new compounds were confirmed by spectroscopic methods and microanalyses. Preliminary bioassays indicated that some compounds showed fungicidal activity against Puccinia tritinia and PGR activity as well.     

Syntheses, Spectral Studies and Bioanalyses of Some Triorganotin(Ⅳ) Complexes of Cephlaxine

Five novel triorganotin(Ⅳ) complexes have been synthesized by refluxing trimethyl, triethyl, tributyl, triphenyl and tribenzyltin chloride with Cephlaxine.These compounds were characterized by spectroscopic (IR,1H, 13C, 119Sn NMR) techniques and elemental analysis.The results obtained through these techniques are in full agreement with the proposed 1:1 stoichiometry.The synthesized compounds were than tested against various microorganisms and fungi.The results of new products obtained showed that the triphenyltin(IV) complex displayed promising activity against all types of bacteria and fungi used while all other compounds showed significant antibacterial and antifungal activity.     

Comparative structural and fungicidal studies of Mono-methyl phthalate and its Tin(IV) derivatives

The results of an investigation into the fungicidal properties of some organotin(IV) compounds with Mono-methyl phthalate are reported. The compounds were characterized by various spectroscopic techniques including ¹H-¹³C-¹¹⁹Sn-NMR, FT-IR, and ¹¹⁹Sn Mössbauer studies. On the basis of these techniques, all the complexes show penta coordination with a trigonal bipyramidal environment around the tin. The synthesized compounds were tested against a number of plant pathogenic fungi. The fungicidal data reveal that the tri-phenyltin(IV) compound proves to be a powerful fungicide. Comparison between the fungicidal activity of the trialkyltin(IV) compounds shows that the tri-phenyl tin(IV) complex is most active against all plant pathogens; the rest of the complexes also exhibit significant antifungal activity but less than the former one.     

A novel class of 1,4-disubstituted 1,2,3-triazoles: Regioselective synthesis,antimicrobial activity and molecular docking studies

A Novel class of 1,4-disubstituted 1,2,3-triazoles have been synthesized in good to excellent yields via Cu(I) accelerated azide-alkyne click chemistry reaction strategy. The newly synthesized compounds were assessed for their in vitro antimicrobial activity against five Gram-positive, seven Gram-negative bacteria and three fungi. Most of the synthesized compounds displayed significant activity against the tested Gram-positive and Gram-negative bacteria. Molecular docking study revealed that all docked compounds are bound efficiently with the active site of Topoisomerase IV (4EMV) receptor with the observed the free energy of binding from −7.79 to −9.44 kcal/mol. Interestingly, compound 13a forms four hydrogen bonds and displayed high binding energy (−9.44 kcal/mol) with the Topoisomerase IV (4EMV) receptor which correlated with their in vitro antimicrobial assays.     

Synthesis of certain 2-substituted-1H-benzimidazole derivatives as antimicrobial and cytotoxic agents

A series of 2-substituted-1H-benzimidazole derivatives were synthesized and evaluated for antimicrobial, antifungal and cytotoxic activities. The results showed that all tested compounds showed potent antimicrobial activity against some species of Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli, Salmonella typhi) and fungi (Candida albicans) with minimum inhibitory concentrations (MICs) lower than 0.016 μg/mL. In contrast, all tested compounds were inactive against Staphylococcus aureus (Gram-positive bacterium). The final targets were also tested for their antitumor activity in vitro on cervical carcinoma (HeLa) cell line. Eight of the test compounds displayed more potent cytotoxic effect than doxorubicin at nanomolar concentrations. Compounds 2c and 3c exerted the strongest cytoyoxic effect with IC(50) 15 and 13 nM, respectively.     

Synthesis and biological activities of novel 2-amino-1,3-thiazole-4-carboxylic acid derivatives

A series of novel 2-amino-1, 3-thiazole-4-carboxylic acid derivatives were designed and synthesized. Their structures were confirmed by melting points, IR, ¹H NMR, ¹³C NMR, and HRMS or elemental analysis. Biological activities of all title compounds including fungicidal activity and antivirus activity were evaluated systematically. Preliminary bioassays indicated that these compounds exhibited good fungicidal activity at 50 μg/mL, compounds 4b and 4i exhibited over 50% activity against six fungi tested. Most compounds showed good activity against TMV with different models in vivo at 100 μg/mL. Compounds 4c and 4e stood out with high effects against TMV in vivo in all models tested, including protective, inactivative, curative, and inductive activities. These data demonstrate a new strategy for fungi and virus control.     

In vitro antimicrobial studies of naphthalen-1-ylmethyl substituted silver N-heterocyclic carbene complexes

Seven novel naphthalen-1-ylmethyl substituted silver N-heterocyclic carbene (Ag–NHC) complexes (1–7) were synthesized by the interaction of benzimidazolium salts with silver carbonate in dry dichloromethane at room temperature and characterized by means of spectroscopic methods and elemental analysis techniques. The Ag–NHC compounds were tested for their in vitro antibacterial and antifungal activity against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Enterococcus faecalis, Candida albicans and Candida tropicalis and showed high antimicrobial activities. The synthesized complexes, in particular, demonstrated better results against both fungi and gram-positive bacteria.     

Synthesis and fungicidal activity of aryl(arylamino)methylphosphonic acids

A series of aryl(arylamino)methylphosphonic acids were synthesized based on the previous work for the modification of alkylphosphonates. As key intermediates, α-aminophosphonates were synthesized with high yield by a three-component Kabachnik–Fields reaction under solvent-free conditions. The compounds were identified and characterized by infrared, ¹H NMR, ¹³C NMR, mass spectrum, and elemental analyses. Their fungicidal activities against typical fungi occurring in the Chinese agro-ecosystems were evaluated. The results of preliminary bioassays showed that some of the title compounds exhibited moderate fungicidal activities against tomato late blight and cucumber fusarium wilt. For example, compound 3b showed 78% inhibitory activity against tomato late blight, and compound 3h possessed 86% inhibitory activity against cucumber fusarium wilt.