Synthesis and Antibacterial Activity of Novel 4″‐O‐Carbamoyl Erythromycin‐A Derivatives

Novel 4″‐O‐carbamoyl erythromycin‐A derivatives were designed, synthesized, and evaluated for their in‐vitro antibacterial activities. All of the 4″‐O‐carbamoyl derivatives showed excellent activity against erythromycin‐susceptible Staphylococcus aureus ATCC25923, Streptococcus pyogenes, and Streptococcus pneumoniae ATCC49619. Most of the 4″‐O‐arylalkylcarbamoyl derivatives displayed potent activity against erythromycin‐resistant S. pneumoniae encoded by the mef gene and greatly improved activity against erythromycin‐resistant S. pneumoniae encoded by the erm gene or the erm and mef genes. In particular, the 4″‐O‐arylalkyl derivatives 4c–4e and 4g were found to possess the most potent activity against all the tested erythromycin‐susceptible strains, which were comparable to those of erythromycin, clarithromycin, or azithromycin. 4″‐O‐Arylalkyl derivatives 4e and 4g were the most effective against erythromycin‐resistant S. pneumoniae encoded by the mef gene (0.25 and 0.25 µg/mL). 4″‐O‐Arylalkyl derivatives 4a and 4b exhibited significantly improved activity against erythromycin‐resistant S. pneumoniae encoded by the erm gene. In contrast, the 4″‐O‐alkylcarbamoyl derivatives hardly showed improved activity against all the tested erythromycin‐resistant strains.     

Antifungal and Antibacterial Activity of the Newly Synthesized 2‐Xanthone Derivatives

A series of 2‐substituted xanthone derivatives 8 – 20 containing selected allyl, cinnamyl, morpholine, and imidazole moieties were synthesized and tested for their antifungal and antibacterial in‐vitro properties. Of the newly synthesized derivatives, ten revealed antifungal activity especially against Trichophyton mentagrophytes (the biggest inhibition zones ranged 35 mm for 11 and 13 ). 2‐(3‐(Allylamino)propoxy)‐9H‐xanthen‐9‐one hydrochloride 9 inhibited growth of all of the examined fungal species. Significant efficacy against evaluated yeasts and dermatophytes was also observed for 6‐chloro‐2‐methyl‐9H‐xanthen‐9‐one derivatives 11 – 13 containing encyclic amine moieties. Additionally, compounds 9 , 11 , and 12 hindered development of bacteria species but in a lesser degree. They were efficacious against Staphylococcus aureus, Escherichia coli, and Enterococcus faecalis.     

Synthesis,In Vitro Antimicrobial and Antioxidant Activities of Some New 4,5‐Dihydro‐1H‐1,2,4‐triazol‐5‐one Derivatives

A series of compounds derived from 4,5‐dihydro‐1H‐1,2,4‐triazol‐5‐one were synthesized and characterized by spectral data. The 12 new compounds were analyzed for their potential in vitro antioxidant activities by three different methods. Compound 4f showed the best activity for the iron binding. In addition, the compounds 4 were titrated potentiometrically with tetrabutylammonium hydroxide in non‐aqueous solvents. The RP‐HPLC capacity factors (k′) of the series were also determined on a C18 column, with methanol/water as the mobile phase. The correlation between log k′ with the percentage of methanol in the mobile phase was used for the determination of the log k_w values for these compounds. The antimicrobial activities of these compounds were also screened against bacteria and yeast.     

Synthesis and Antimicrobial Activity of Some Novel 2‐[4‐(Substituted Piperazin‐/Piperidin‐1‐ylcarbonyl)phenyl]‐1H‐benzimidazole Derivatives

In this study, we report the synthesis and antimicrobial evaluation of several new 4‐(1H‐benzimidazol‐2‐yl)benzamides ( 11 – 30 ) and 5‐chloro‐1‐(p‐fluorobenzyl)‐2‐{4‐[(4‐methylpiperazin‐1‐yl)carbonyl]phenyl}‐1H‐benzimidazole ( 33 ). Compound 20 exhibited the best antibacterial activity with MIC value of 6.25 μg/mL against Staphylococcus aureus and methicillin‐resistant Staphylococcus aureus (MRSA). Significant antifungal activities were obtained with the compounds 13 , 14, 18 , 19, and 33 with MIC values of 3.12 μg/mL which are close to fluconazole.     

Novel Carboline Derivatives as Potent Antifungal Lead Compounds: Design,Synthesis, and Biological Evaluation

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Novel 3,6‐Disubstituted 7H‐1,2,4‐Triazolo[3,4‐b][1,3,4]thiadiazines: Synthesis,Characterization, and Evaluation of Analgesic / Anti‐inflammatory,Antioxidant Activities

In this study, the synthesis of a new series of 3,6‐disubstituted‐7H‐1,2,4‐triazolo[3,4‐b][1,3,4]thiadiazine 1a – 4c compounds derived from 4‐amino‐3‐substituted‐1,2,4‐triazole‐5‐thiones 1 – 4 is described. All of the synthesized compounds were screened for their possible analgesic / anti‐inflammatory, antioxidant activities and gastric toxicity. The compound 2c was found to have both significant analgesic and consistent anti‐inflammatory activity without inducing any gastric lesions along with minimal lipid peroxidation. A deep insight into the structures of the active compounds revealed that the compounds carrying an electron withdrawing group (a chloride or fluoride) on the phenyl ring at 6‐position of the condensed heterocyclic derivatives exhibited noticeable higher activity.     

Synthesis and Antibacterial Activity of a Novel Series of 2,3‐Diaryl‐substituted‐imidazo(2,1‐b)‐benzothiazole Derivatives

Benzothiazole and imidazole compounds are extensively studied heterocyclics due to their wide spectrum of bioactivities. Among them, the imidazo(2,1‐b)‐benzothiazole derivatives are pharmacologically important because of their immunostimulant, anti‐inflammatory, antifungal, antimicrobial, antitumor, and other activities. In the present research work, a novel series of 2,3‐diaryl‐substituted imidazo(2,1‐b)‐benzothiazoles 13a–o have been synthesized by reaction of substituted 2‐aminobenzothiazoles 1–8 and an appropriately substituted α‐bromo‐1‐(4′′‐substituted)‐phenyl‐2‐(4′‐substituted)‐phenyl‐1‐ethanones 9–12 in the presence of anhydrous acetonitrile. They were characterized by physicochemical, elemental, and spectral (IR, ¹H‐NMR, and Mass) data. All the synthesized compounds were screened for their in‐vitro antibacterial activity against Gram‐positive, Gram‐negative bacteria. The investigation of antibacterial screening data revealed that most of the compounds tested have demonstrated congruent activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa as compared with the standard ampicillin. Among the series, compounds 13d , 13h , and 13m exhibited excellent an antibacterial activity profile as compared with the standard. In summary, preliminary results indicate that some of the newly synthesized title compounds exhibited promising antibacterial activities and they warrant more consideration as prospective antimicrobials.     

Microwave Assistant One Pot Synthesis,Crystal Structure,Antifungal Activities and 3D‐QSAR of Novel 1,2,4‐Triazolo[4,3‐a]pyridines

A series of novel 1,2,4‐triazolo[4,3‐a]pyridines were synthesized, and their structures were characterized by ¹H NMR, MS, elemental analysis, and single‐crystal X‐ray diffraction analysis. The antifungal activities were evaluated. The antifungal activity results indicated that the compound 2b , 2g , 2p , and 2i exhibited good activities. The activity of compound 2b , 2g , 2p , and 2i can compare with the commercial pesticide. The 3D‐QSAR model was developed using CoMFA method. Both the steric and electronic field distributions of CoMFA are in good agreement in this work and will be very helpful in designing a new set of analogues.     

Design,Synthesis, and Biological Evaluation of 1,5‐Diaryl‐1,2,4‐triazole Derivatives as Selective Cyclooxygenase‐2 Inhibitors

A series of 1,5‐diaryl‐1,2,4‐triazole derivatives were synthesized and evaluated as cyclooxygenase‐2 (COX‐2) inhibitors. The results of the preliminary biological assays in vivo showed that eight compounds 5b , 6b , 6c , 7c , 8b , 8d , 9c , and 9d have potent anti‐inflammatory activity (P < 0.01), while compounds 6b , 6c , and 9c exhibit marked potency. Compound 6c was then selected for further investigation. In the COX inhibition assay in vitro, compound 6c was identified as a potent and selective inhibitor of COX‐2 (COX‐2 IC₅₀ = 0.37 µM; SI = 0.018), being equipotent to celecoxib (COX‐2 IC₅₀ = 0.26 µM; SI = 0.015). In a rat carrageenan‐induced paw edema assay, 6c exhibited moderate anti‐inflammatory activity (35% inhibition of inflammation) at 2 h after administration of 15 mg/kg as an oral dose. A docking study also revealed that compound 6c binds in the active site of COX‐2 in a similar mode to that of the known selective COX‐2 inhibitor SC‐558.     

6,8-二氯硫色满酮衍生物的合成及抗真菌活性(英)

本文设计并合成了一系列6,8-二氯硫色满酮衍生物。其中12个为未见文献报道的新化合物。对所合成的化合物进行了体外抑菌活性试验,其结果表明某些化合物对6种供试真菌有较好的抑制作用。     

6，8—二氯硫色满酮衍生物的合成及抗真菌活性

本文设计并合成了一系列6,8－二氯硫色满酮衍生物,其中12个为未见文献报道的新化合物,对所合成的化合物进行了体外抑菌活性试验,其结果表明某些化合物对6种供试真菌有较好的抑制作用。     

Synthesis and Biological Evaluation of Kojic Acid Derivatives Containing 1,2,4‐triazole as Potent Tyrosinase Inhibitors

A series of 5‐substituted‐3‐[5‐hydroxy‐4‐pyrone‐2‐yl‐methymercapto]‐4‐amino‐1,2,4‐triazole derivatives were synthesized by nucleophilic substitution reaction of 5‐hydroxy‐2‐chloromethyl ‐4H‐pyran‐4‐one with 5‐substituted‐3‐mercapto‐4‐amino‐1,2,4‐triazole, and their inhibitory effects on mushroom tyrosinase were evaluated. The results indicated that most of the synthesized compounds exhibited significant inhibitory activity. Specifically, 5‐(4‐chlorophenyl)‐3‐[5‐hydroxy‐4‐pyrone‐2‐yl‐methymercapto]‐4‐amino‐1,2,4‐triazole ( 6j ) exhibited the most potent tyrosinase inhibitory activity with IC₅₀ value of 4.50 ± 0.34 μm . The kinetic studies of the compound ( 6j ) demonstrated that the inhibitory effects of the compound on the tyrosinase were belonging to competitive inhibitors. Meanwhile, the structure–activity relationship was also discussed.     

Facile Synthesis and Antibacterial,Antitubercular, and Anticancer Activities of Novel 1,4‐Dihydropyridines

A series of twenty new 4‐substituted‐2,6‐dimethyl‐3,5‐bis‐N‐(heteroaryl)‐carbamoyl‐1,4‐dihydropyridines have been prepared from a three‐component one‐pot condensation reaction of N‐heteroaryl acetoacetamide, an aromatic/heteroaromatic aldehyde, and ammonium acetate under four different experimental conditions. Except for the conventional method, all the experimental conditions were simple, eco‐friendly, economical, and the reactions were rapid and high‐yielding. The methods employed have been compared in terms of yields, cost, and simplicity. The synthesized compounds were characterized by different spectroscopic techniques and evaluated for their in‐vitro anticancer, antibacterial, and antitubercular activities. Amongst the compounds tested, compound 25 exhibited the highest anticancer activity while compounds 14 and 18 exhibited significant antibacterial and antitubercular activities.     

3‐Imidazolyl‐Substituted Flavans as Potential Antifungal Agents: Synthesis,Stereochemical Properties,and Antifungal Activity

A new series of 3‐imidazolyl‐substituted flavan derivatives being equipped with a N‐(phenethyl)‐azole scaffold as the common pharmacophore of azole antifungals, were synthesized. The stereochemical and conformational properties of compounds were also characterized by ¹H‐NMR data. The results of the antifungal evaluation of trans‐3‐imidazolyl‐substituted flavan‐4‐ones and (Z)‐trans‐3‐imidazolyl‐substituted flavan‐4‐one oximes in comparison with the reference drug fluconazole indicated that most target compounds possessed significant in‐vitro antifungal activities against the tested fungi, comparable or superior to fluconazole.     

Synthesis,in‐vitro Antimicrobial and Cytotoxic Studies of Novel Azetidinone Derivatives

Developing novel antimicrobial drugs is increasingly important in the modern pharmaceutical industry. A series of novel 3‐chloro‐4‐[4‐(2‐oxo‐2H‐chromen‐4‐ylmethoxy)phenyl]‐1‐phenylazetidin‐2‐ones 5a–o have been synthesized from 4‐bromomethylcoumarins 1a–e and 4‐aryliminomethyl‐phenols 3a–c . These compounds were screened for their in‐vitro antibacterial activity against two Gram‐positive (Staphylococcus aureus and Vancomycin resistant enteroccoccus) and two Gram‐negative (Escherichia coli and Shigella dysentery) bacterial strains and antifungal activity against Aspergillus fumigatus, Candida albicans, and Penicillium. Results revealed that compounds 5c , 5f , 5h , 5j , and 5m showed excellent activity against a panel of microorganisms. The brine‐shrimp bioassay was also carried out to study their in‐vitro cytotoxic properties and two compounds, 5h and 5m , possessing LD₅₀ = 7.154×10^–4 M and 5.782×10^–4 M, respectively, displayed potent cytotoxic activity against Artemia salina. The presence of a chlorine group in the coumarin moiety, its effect on their antibacterial, antifungal, and cytotoxic activities is discussed. All newly synthesized compounds were characterized by elemental analysis, IR, ¹H‐NMR, ¹³C‐NMR, and MS.