Synthesis and Antimicrobial Studies of Organophosphates Derived From 2-(2″-Hydroxynaphthyl)Benzoxazole

Abstract

A series of biologically active phenoxy derivatives of 2-substituted benzoxazole organophosphates have been synthesized by the reaction of O-(naphthyl benzoxazolyl-2-) phosphorodichloridate/phosphorodichloridothioate with phenol/4-chlorophenol/4-nitroph- enol in 1:1 and 1:2 molar ratios. These compounds have been characterized on the basis of elemental analysis, IR, ¹H NMR, ³¹P NMR, and mass spectral studies. The antibacterial activity of these 2-substituted benzoxazole phenoxy derivatives has been evaluated against pathogenic bacteria Staphylococcus aureus (+ve) and Escherichia coli (?ve). The antifungal activity of these 2-substituted benzoxazole phenoxy derivatives has been evaluated against pathogenic fungi Aspergillus niger and Fusarium oxysporium. All compounds were found to have significant antibacterial and antifungal activity.     

CAN catalyzed one-pot synthesis and docking study of some novel substituted imidazole coupled 1,2,4-triazole-5-carboxylic acids as antifungal agents

The present work describes a facile,one-pot three component synthesis of a series of 3-[(4,5-diphenyl-2-substituted aryl/heteryl)-1H-imidazol-1-yl]-1H-1,2,4-triazole-5-carboxylic acid derivatives M(1-15).Benzil,aromatic aldehydes and 3-amino-l,2,4-triazole-5-carboxylic acid was refluxed in ethanol using cerric ammonium nitrate(CAN) as a catalyst to give the title compounds in good yields.The compounds were evaluated for their in vitro antifungal and antibacterial activity.Compounds M1,M9,and M15 were found to be equipotent against Candida albicans when compared with fluconazole.Compounds M2.M5,and M14 showed higher activity against Streptococcus pneumoniae.Escherichia coli and Streptococcus pyogenes,respectively,compared with ampicillin.Docking study of the newly synthesized compounds was performed,and the results showed good binding mode in the active sites of C albicans enzyme cytochrome P450 lanosterol 14α-demethylase.The results of in vitro antifungal activity and docking study showed that synthesized compounds had potential antifungal activity and can be further optimized and developed as a lead compound.     

3-Thiolated 2-azetidinones: synthesis and in vitro antibacterial and antifungal activities

A series of 3-thiolated β-lactams were synthesized by [2+2] ketene-imine cycloaddition reaction from S-substituted mercaptoacetic acids and Schiff bases. Then, some of the 3-methylthio β-lactams were converted to 3-(methylsulfinyl) β-lactams and 3-(methylsulfonyl) β-lactams using m-CPBA under different reaction conditions. All the compounds were characterized by spectral data and elemental analyses and were evaluated for their in vitro antibacterial and antifungal activities against pathogenic strains including Staphylococcus aureus (Methicillin resistant strain). The preliminary screening results indicated that some of these compounds demonstrated moderate to very good antibacterial and antifungal activities.     

Synthesis, antimicrobial and antifungal activity of double quaternary ammonium salts of biphenyls

The synthetic methods for new 2-, 2,2′-, and 3-substituted 4,4′-bis(chloromethyl)biphenyls were developed. Quaternization of them with various amines resulted in a series of new double quaternary ammonium salts containing the biphenyl moiety. The majority of the obtained compounds have a pronounced antifungal and antibacterial activity against the Gram-positive bacteria.     

哒嗪酮类新衍生物的合成及其对血小板聚集的抑制作用

6-(4-取代苯基)哒嗪酮类衍生物具有较强的抑制血小板聚集作用.设计并合成了6-(4-取代苯基)-5-甲基-4,5-二氢-3(2H)哒嗪酮类化合物.以乙酰苯胺为原料,经付-克酰化反应、氰化、水解、水合肼环化反应合成目标化合物,并参考Born方法进行体外药理实验.目标化合物通过1H NMR,MS,IR,元素分析等证实了其结构.体外药理实验表明,目标化合物对二磷酸腺苷(ADP)诱导的人血小板聚集均有较强的抑制作用.     

Salicylanilide acetates: synthesis and antibacterial evaluation

A new series of salicylanilide acetates was synthesized and evaluated for their in vitro antifungal and antituberculotic activity. Some of the evaluated compounds possessed comparable or better antifungal activity than a fluconazole standard. All these compounds exhibited very good potential and their in vitro activity against drug resistant and sensitive clinical isolates of Mycobacteria were found to be equivalent or better than a standard of isoniazide, a well-known first-line drug for tuberculosis treatment.     

Synthesis and biological activity of novel N-(3-furan-2-yl-1-phenyl-1H-pyrazol-5-yl) amides derivatives

A series of novel N-(3-furan-2-yl-1-phenyl-1H-pyrazol-5-yl) amides derivatives were designed and synthesized. Their structures were confirmed by ¹H NMR, ¹³C NMR and HRMS. All title compounds were evaluated for their herbicidal and antifungal activities. Preliminary bioassay results indicated that the title compounds showed good to moderate herbicidal activity at 1000 mg/L. Compound 6q presented the best activity against Digitaria sanguinalis (L) Scop., Amaranthus retroflexus L. and Arabidopsis thaliana with an inhibition degree of five. Compound 6d also showed an inhibition degree of five against D. sanguinalis. In addition, at 50 mg/L, most compounds exhibited good in vitro antifungal activity against Sclerotinia sclerotiorum, with compound 6c showing over 90% antifungal activity against S. sclerotiorum and Pellicularia sasakii.     

Synthesis,antimicrobial and anti-inflammatory activities of some novel 5-substituted imidazolone analogs

In view of potent antimicrobial and anti-inflammatory activities exhibited by 5-substituted imidazolones, a variety of novel imidazolone analogs 3a-l were synthesized by the condensation of different substituted oxazolones 1 with various aromatic amines 2. All the synthesized compounds were screened for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Several analogs produced good or moderate activities particularly against the tested Gram-positive bacteria Micrococcus luteus and Gram-negative bacteria Pseudomonas aeruginosa and. Meanwhile, compounds 3b and 3c displayed marked antifungal activity against C. albicans. In addition, the in vivo anti-inflammatory activity of the synthesized compounds was determined using the carrageenin-induced paw oedema method in rats. Two of 5-substituted imidazolone derivatives, 3k and 3d show good anti-inflammatory activity. The structures of all the newly synthesized compounds were elucidated using IR, ¹H NMR and ¹³C NMR.     

Design,synthesis and biological evaluation of novel N1,N8-bis(((4-((5-aryl-1,3,4-oxadiazol-2-yl)methoxy)phenyl)amino)oxy)-1-naphthamide derivatives

A new series of 1,8-bis(4-((5-phenyl-1,3,4-oxadiazol-2-yl) methoxy)-substituted aryl) naphthalene-1,8-dicarboxamide derivatives (6a–j) were synthesized in the presence of POCl₃ and obtained good yields. All the synthesized novel compounds were characterized by IR, ¹H NMR, ¹³C NMR, HRMS spectroscopic data and elemental analysis. All the synthesized compounds evaluated for their antibacterial and antifungal activities. The antibacterial activity screened against Gram-positive bacteria Staphylococcus aureus and Gram-negative bacteria Escherichia coli and used standard reference drug ciprofloxacin. The antifungal activity screened against two pathogenic fungal strains Aspergillus niger and Candida albicans used a reference standard drug Voriconazole. All these compounds (6a–j) demonstrate good antibacterial and antifungal activity. Among them, compounds 6h and 6c show highest antibacterial and antifungal activity.     

Studies on Antifungal Agents. Part 22. 3-aryl-5-[(aryloxy)alkyl]-3-[(1H-imidazol-1-yl)methyl]-2-methylisoxazolidines and related derivatives

The synthesis and antifungal activity of a novel series of 3-aryl-5-[(aryloxy)alkyl]-3-[(1H-imidazol-1-yl)-methyl]-2-methylisoxazolidines and related compounds, are discussed. The synthesis of the title compounds was accomplished via a 1,3-dipolar cycloaddition of α-substituted ketonitrones with l-alkenyl phenyl ethers (Scheme 2 and 3). The compounds were evaluated for in vitro antifungal activity in solid agar cultures against a broad variety of yeast and systemic mycoses and dermatophytes. While antifungal activity was evident throughout the series, in general, derivatives having halogen atom(s) in either or both aryl rings demonstrated the highest potency, especially against Trichophyton rubrum and Candida albicans. The dichloro analog 20 (PR 967-248) was found to possess the most useful activity. Its minimum inhibitory concentration (MIC) values ranged between 0.2 and 2.0 μg/ml, as compared to 0.2–20.0 μg/ml for the standard drug ketoconazole (4).     

Synthesis and Antibacterial and Antifungal Properties of Novel S-, N-, N,S-, and S,O-Substituted 1,4-Naphthoquinone Derivatives

Abstract

A novel series of substituted 1,4-naphthoquinone derivatives were synthesized and evaluated for their antibacterial and antifungal activity. The structures of the novel products were characterized by spectroscopic methods. Among the tested compounds, 2,2′,3,3′-alkoxy substituted naphthoquinones, S,O-substituted naphthoquinone, and N,S-substituted naphthoquinone derivatives are the most potent antifungals against C. tenuis. 2,3-Thio-2′,3′-alkoxy substituted naphthoquinones are the most effective antifungal compounds against A. niger.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Synthesis, characterization, antibacterial and antifungal evaluation of novel monosaccharide esters

A novel series of 3-(2-furyl)acrylate monosaccharide esters Ia–f and menthyloxycarbonyl monosaccharide esters IIa–f were designed and synthesized. The chemical structures of the target compounds were confirmed by IR, 1H- and 13C-NMR and ESI-MS, and the target compounds were investigated for their in vitro antibacterial and antifungal activities. The antibacterial screening results showed that the 3-(2-furyl)acrylate monosaccharide ester derivatives Ia–f were either inactive or only weakly active against the three Gram-positive bacterial strains tested, whereas the menthyloxycarbonyl monosaccharide ester derivatives IIa–f exhibited higher levels of activity, with compound IIe being especially potent. The results of the antifungal screening revealed that compounds Ib, Ie, IIb and IIc displayed potent in vitro activities, whereas If and IIf showed promising activities against all of the microorganisms tested, with If exhibiting levels of activity deserving of further investigation.     

Synthesis and biological evaluation of novel triazole derivatives as antifungal agents

A series of 1-(benzylamino)-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-l-yl)propan-2-ols compounds were synthesized and evaluated for their antifungal activities in vitro.The results showed that compounds 6A and 6B exhibited good antifungal activity.Compound 6A8 showed the strongest antifungal activity,which was significantly higher than that of the lead compounds and positive-control drugs Fluconazole and Itraconazole.In particular,the antifungal activity of compound 6A8 against Candida albicans and Candida krusei(MIC80 both at 0.00097μg/mL) was 515 and 64 times that of Fluconazole,respectively.The structure-activity relationships of the synthesized compounds were discussed,and the docking model of the target compounds with fungal lanosterol 14α-demethylase (CYP51) was analyzed.     

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.     

Synthesis and antifungal activity of d-glucopyranosyl ureas and d-glucofurano-imidazolidine-2-ones

A series of N-β-d-glucopyranosyl-N’-substituted phenyl ureas were synthesized by reaction of glucosyl isocyanate with arylamines and glycosamine with aryl isocyanates, and a series of d-glucofurano-imidazolidine-2-ones were obtained via deacetylation of glycosylureas. Although some of the compounds have already been described, most were prepared for the first time in this work. The structures of all the compounds synthesized were confirmed by IR, ¹H NMR, and, in part, by ¹³C NMR. Antifungal activity of the title compounds was determined against four kinds of plant pathogenic fungi, Sclerotinia sclerotiorum, Fusarium graminearum, Fusarium oxysporum, and Bipolaris maydis. Preliminary bioassay indicates that most of glycosylureas had some activity against S. sclerotiorum; for some, the antifungal activity was strong. However, most of the imidazolidine-2-ones had weak antifungal activity.     

Preparation of 7-substituted pyrrolo [2,3-d] pyrimidines and 9-substituted purines as potential antiparasitic agents

A series of six 7-substituted pyrrolo [2, 3-d] pyrimidines and two 9-substituted purines were prepared and evaluated for potential antiparasitic activity. All were inactive against P. berghei in mice. Six of the target compounds were also evaluated for antitrypanosomal activity against T. rhodesiense in mice. All six compounds were also inactive in this screen.     

Design,Synthesis and Antitumor Activity in vitro of a Series of 3-Arylcoumarins

A new series of 7-substituted 3-arylcoumarins was designed, synthesized and evaluated as novel antitumor agents in vitro. It was found that several compounds of them exhibit activity in vitro against SK-HEP-l（hepatocellular carcinoma）, HepG2（hepatocellular carcinoma） and SGC7901（gastric carcinoma） cell lines to some extent. Moreover, compounds 5a, 5b, 6a and 6b have better activity against HeLa（cervical carcinoma） cell and their half maximal inhibitory concentration（IC50） values are less than 10μmol/L.     

Synthesis and biological evaluation of novel 2-(substituted isoxazol-4-yl)-5-arylamino-1,3,4-oxadiazoles

A series of 2-(5-methyl-3-(4-chloro/trifluoromethylphenyl)isoxazol-4-yl)-5-arylamino-1,3,4-oxadiazoles were synthesized from 4-chloro/trifluoromethyl benzaldehyde, ethyl acetoacetate, hydroxylamine hydrochloride, hydrazine hydrate, and aryl isocyanate by multi-step reactions. The structures of the target compounds were elucidated by IR, ¹H NMR, MS, and elemental analysis. All these compounds were tested for in vitro antifungal activities against Botrytis cinerea and Rhizoctonia cerealis by the mycelium growth rate method, and the results indicated that some compounds displayed high antifungal activity against Botrytis cinerea.     

Synthesis,docking and ADMET prediction of novel 5-（（5-substituted- 1 -H- 1,2,4-triazol-3-yl ） methyl ）-4, 5,6,7-tetrahydrothieno [ 3,2-c ] pyri- dine as antifungal agents

A novel series of 5-((5-substituted-1H-1,2,4-triazol-3-yl)methyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridines 5(a–i) has been synthesized from thienopyridine hydrazide, substituted aromatic nitriles using 4-dimethylaminopyridine(DMAP) as a catalyst under microwave irradiation and evaluated for their in vitro antifungal activity. Compound 5g is found to be more potent against Candida albicans when compared with miconazole. Docking study of the newly synthesized compounds was performed, and results showed good binding mode in the active site of fungal enzyme P450 cytochrome lanosterol 14 ademethylase. ADMET properties of synthesized compounds were also analyzed and showed good drug like properties. The results of in vitro antifungal activity, docking study and ADMET prediction revealed that the synthesized compounds have potential antifungal activity and can be further optimized and developed as a lead compound.     

Synthesis and antitumor activity of novel pyrimidinyl pyrazole derivatives. III. Synthesis and antitumor activity of 3-phenylpiperazinyl-1-trans-propenes

A series of novel 3-[4-phenyl-1-piperazinyl]-1-[5-methyl-1-(2-pyrimidinyl)-4-pyrazolyl]-1-trans-propenes and related compounds were synthesized and evaluated by their cytotoxic activity against several tumor cell lines in vitro and in vivo antitumor activity against some tumor models when administered both intraperitoneally and orally. Compounds with the 3-chloropyridin-2-yl group (9g) and the 3-fluoro-5-substituted phenylpiperazinyl group (29b, c, and e) showed significantly potent cytotoxicity by in vitro testing. Among them, the 3-cyano-5-fluorophenyl derivative (29b) exhibited potent antitumor activity against several tumor cells including human carcinoma without causing undesirable effects in mice.