Synthesis of novel 1,2,3-thiadizoles and 1,2,3-selenadiazoles as new antimicrobial agents

Abstract

A series of novel 1,2,3-thiadiazoles and 1,2,3-selenadiazoles having a long alkyl chain were synthesized by reacting semicarbazones with SOCl₂ and SeO₂, respectively. The structures of the target compounds 5–12 were confirmed by spectroscopy (IR, ¹H NMR, ¹³C NMR, and MS) and elemental analysis. Their antibacterial and antifungal activities were evaluated against six bacteria (Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis, Staphylococcus epidermidis, Staphylococcus aureus) and three fungi (Candida albicans, Candida parapsilosis, Candida tropicalis). The results of bioassays indicated that the compounds 5-Dodecyl-4-(4-methoxy-phenyl)-[1-3]selenadiazole (7), 4-Methyl-5-tetradecyl-[1-3]selenadiazole (8) and 5-Dodecyl-4-(4-methoxy-phenyl)-[1-3]thiadiazole (11) displayed moderate antibacterial activity against S. Epidermidis. On the other hand, according to antifungal screening results, compounds 5-Dodecyl-4-phenyl-[1-3]selenadiazole (5), 4-p-Tolyl-5-undecyl-[1-3]selenadiazole (6), and 5-Dodecyl-4-(4-methoxy-phenyl)-[1-3]selenadiazole (7) exhibited significant antifungal activities studied yeast strains.     

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.     

Synthesis and Evaluation of Antimicrobial Activity of Some New Hetaryl‐Azoles Derivatives Obtained from 2‐Aryl‐4‐methylthiazol‐5‐carbohydrazides and Isonicotinic Acid Hydrazide

A series of new 1,3,4‐oxadiazole/thiadiazole and 1,2,4‐triazole derivatives have been synthesized starting from 2‐aryl‐4‐methylthiazol‐5‐carbohydrazides and isonicotinic acid hydrazide. All the newly synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR, and mass spectrometry. The synthesized compounds were screened for their antibacterial and antifungal activity, assessed as growth inhibition diameter. Some of them showed good antibacterial activity against gram positive Staphylococcus aureus, while the antibacterial activity against Listeria monocytogenes, Escherichia coli, and Salmonella typhymurium and antifungal activity against Candida albicans was modest. None of the tested compounds showed inhibitory activity against gram positive bacteria Enterococcus faecalis and Bacillus cereus and against gram negative bacteria Pseudomonas aeruginosa.     

Selective extraction of toxic heavy metals and biological activity studies using pyrimidylthioamide functionalised calix[4]arene

The current study comprises synthesis of pyrimidylthioamide derivatized calix[4]arene (5), and its comparative liquid–liquid extraction properties with the compound 4 towards the selected transition metal ions (Cu²⁺, Co²⁺, Ni²⁺, Pb²⁺, Hg²⁺ and Cd²⁺) were investigated. Experimental results revealed that the compound 5 shows better efficiency and affinity for Pb²⁺ and Hg²⁺ ions as compared to compound 4. The antibacterial and antifungal effects of compound 5 were also investigated on various bacteria and fungi. It has been observed that compound 5 has some effects against Salmonella typhimurium NRRLB 4420, Bacillus cereus ATCC 11778, Staphylococcus aureus NRRL B767 and Bacillus subtilis NRS 744.     

Synthesis and Antimicrobial and Antioxidant Activities of Sulfonamide Derivatives Containing Tetrazole and Oxadiazole Rings

In the present work, we synthesized new sulfonamide derivatives with 1,3,4‐oxadiazole moiety and tetrazole ring. The synthesized derivatives of sulfonamides were characterized through Fourier transform infrared, ¹³C‐APT‐NMR, ¹H‐NMR, and high‐resolution liquid chromatography–mass spectrometry. The biological activities of resulting compound were also investigated and observed that the compounds reveal strong antimicrobial activity over some important bacterial strains including Bacillus subtilis ATCC 6633, Escherichia coli ATCC 25922, Klebsiella pneumoniae ATCC 13883, and Staphylococcus aureus ATCC 29213. The in vitro antifungal properties of synthesized compounds were also a target using Candida albicans NRRL Y‐477 and Saccharomyces cerevisiae fungal strains. We have provided a useful guideline for future studies about the effect of the chemical structures of sulfonamide compounds on the biological activities. Among the target compounds, 7b , 7c , 7d , and 7e demonstrated surprisingly high antimicrobial activities than did others.     

Synthesis and antimicrobial screening of 1,3,4-oxadiazole and clubbed thiophene derivatives

In the present study, a novel series of 2-{5-[4-(1-aza-2-(2-thienyl)vinyl)phenyl](1,3,4-oxadiazol-2-ylthio)}-N-arylacetamides (IV)_1–12 were synthesized and tested for their antimicrobial activity. Newly synthesized compounds were screened for their antibacterial and antifungal activities on Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus pyogenes, Candida albicans, Aspergillus niger and Aspergillus clavatus. The chemical structures of newly synthesized compounds were elicited by IR, ¹H NMR, ¹³C NMR and mass spectral data. The synthesized bio-active compounds exhibited excellent to moderate antimicrobial activity. Compounds (IV)₅, (IV)₆ and (IV)₇ possess excellent antibacterial activity whereas compounds (IV)₆, (IV)₉ and (IV)₁₁ possess excellent antifungal activity.     

Synthesis,spectral, thermal analyses,molecular modeling,and antimicrobial activities of Cu(II)-complexes with 1,3,4-oxadiazole Schiff-base derivatives

Seven Cu(II)-complexes with 2-amino-5-substituted aryl-1,3,4-oxadiazole Schiff bases are presented. The donors and possible geometries of the complexes were investigated by elemental and thermal (differential thermal analysis and thermogravimetric analysis) analyses, molar conductance, magnetic moments, IR, ¹H-NMR, ESR, UV-Vis, and mass spectra. The ligands are bidentate, coordinating through the nitrogen of azomethine and the nearest nitrogen to it. The results are supported by 3-D molecular modeling of 2 using CS Chem 3-D Ultra Molecular Modeling and Analysis Program. The investigated complexes have been screened for in-vitro antibacterial (Escherichia coli and Staphylococcus aureus) and antifungal (Aspergillus flavus and Candida albicans) activities. The qualitative and quantitative antimicrobial activities prove that the complexes are very active against the tested microorganisms.     

Chemical constituents from leaves and trunk bark of Rinorea oblongifolia (Violaceae)

Abstract

Two new coruleoellagic acid derivatives, 3,4′,5,5′,-tetramethylcoruleoellagic acid (1); 3′,4,4′,5,5′-pentamethylcoruleoellagic acid (2) and a new friedelane-type triterpene derivative rinol (5), were isolated from leaves and trunk bark of Rinorea oblongifolia (Violaceae) along with seven known compounds including 3,3′,4,4′,5′-pentamethylcoruleoellagic acid (3), hexamethylcoruleoellagic acid (4), 28-hydroxyfriedelin (6), friedelin (7), friedelan-3-ol (8), scopoletin (9) and β-sitosterol-3-O-β-D-glucopyranoside (10). Their structures were elucidated by means of spectroscopic methods including IR, 1D and 2D NMR in conjunction with mass spectrometry. Crude extracts of leaves and trunk bark as well as compounds 1–4 were evaluated for their antibacterial activities against 7 pathogenic bacterial strains (Streptococcus pneumoniae ATCC49619, Staphylococcus aureus ATCC 43300, Klepsiella pneumoniae ATCC 700603, Haemophilus influenza ATCC 49247, Escherichia coli ATCC 25922, Pseudomonas aeruginosa HM601, Staphylococcus aureus BAA 977). Compound (3) displayed noteworthy activity against Haemophilus influenza with MIC value of 9.38?µg/mL.     

Synthesis,biological screening,in silico study and fingerprint applications of novel 1, 2, 4-triazole derivatives

A series of novel 1,2,4 triazole derivatives were synthesized by treating 4-bromo-2-(4H-1,2,4-triazole-3-yl)aniline (4) with different substituted benzene sulfonyl chlorides 5(a-f) and benzyl bromides 7(a-e) . IR, ¹H-NMR, ¹³C-NMR, and mass analysis confirmed the structures of the newly synthesized compounds. All derivatives were screened for their in vitro antibacterial activity against two bacterial strains viz Escherichia coli and Staphylococcus aureus, antifungal activity against Aspergillus flavus and Candida albicans, anthelmintic activity against Pheretima posthuma and also cytotoxicity activity against MDA-MB 231 and A375 cancer cell lines. It was found that some of the derivatives showed significant antibacterial, antifungal, anthelmintic, and cytotoxic activities when compared to respective standard drugs. Molecular docking studies have assisted the theoretical binding mode of the target molecules. Compounds were also explored for fingerprint application.     

Synthesis of Some N-Alkoxycarbonyl-N″-benzoyl-benzamidrazones（p-toluamidrazones） and 1,3,5-Trisubstituted 1,2,4-Triazole Derivatives from N-Benzoylimidates and their Antimicrobial and Anticancer Screening Studies

Some new N-alkoxycarbonyl-N″-benzoyl-benzamidrazones （p-toluamidrazones） 3a-3d, and 1,3,5-trisubstituted 1,2,4-triazole 4a-4h derivatives by starting from N-benzoylbenzimidates or N-benzoyl-p-toluimidates. The structures of compounds 3 and 4 were established on the basis of elemental analyses, IR, ^1H NMR, ^13C NMR and UV data. Antimicrobial experiments of the compounds performed by using agar-well diffusion and broth microdilution methods revealed that only compounds 3a-3d, 4a and 4b showed inhibitory effect only on Candida albicans ATCC 60193. However, compound 4b had also specific antibacterial activity against Staphylococcus aureus ATCC 25923. The other compounds showed neither antifungal nor antibacterial activities. Compounds 3a, 4a and 4b have been screened on three human tumor cell lines, breast cancer （MCF7）, non small cell lung cancer （NCI-H460）, and CNS cancer （SF-268） at the National Cancer Institute （NCI）, USA, which were found to exhibit low antiproliferative activity.     

Synthesis and Antimicrobial Activity Evaluation of Novel Oxadiazino/Thiadiazino‐Indole and Oxadiazole/Thiadiazole Derivatives of 2‐Oxo‐2H‐benzopyran

A series of novel oxadiazino/thiadiazino‐indole and oxadiazole/thiadiazole derivatives of 2‐oxo‐2H‐benzopyran were synthesized and evaluated for their antimicrobial activities against the bacteria Staphylococcus aureus, Salmonella typhi, and Escherichia coli and two fungal species Candida albicans and Aspergillus niger. The antibacterial activities were expressed as minimum inhibitory concentration (MIC₅₀) in microgram per milliliter. The title compounds 4b and 10b revealed promising antibacterial activity whereas 6d , 7d , 9d , and 10b exhibited significantly impressive antifungal activity.     

Design,synthesis, antimicrobial evaluation,and molecular docking studies of novel symmetrical 2,5-difunctionalized 1,3,4-oxadiazoles

A series of novel symmetrical 2,5-difunctionalized 1,3,4-oxadiazole derivatives of pharmacological significance have been synthesized. The obtained compounds were screened for their in vitro antimicrobial activities against Gram-negative (Escherichia coli and Salmonella typhimurium) and Gram-positive bacteria (Staphylococcus aureus, Enterococcus faecium, and Streptococcus agalactiae or group B Streptococcus), as well as against the fungus Candida albicans. Although the synthesized compounds showed moderate antifungal activity against C albicans, they exhibited good-to-excellent antibacterial activities against several strains, than did standard drugs ampicillin and nystatin. In silico molecular docking in FabI enzyme active site gave information regarding the binding mode of the drug candidate at the molecular level.     

Synthesis and characterization of N′-(11H-indeno[1,2-b]quinoxalin-11-ylidene)benzohydrazonamides as potential antimicrobial agents

Abstract

A series of new N′-(11H-indeno[1,2-b]quinoxalin-11-ylidene)benzohydrazonamides 3a–3j was synthesized in excellent yields from the reaction of N³-substituted benzohydrazonamides 1 and 2-(11H-indeno[1,2-b]quinoxalin-11-ylidene)malononitrile 2 in dichloromethane or with 11H-indeno[1,2-b]quinoxalin-11-one 4 in ethyl acetate at ambient temperature. The new compounds have been characterized and screened for biological activity. Some of them showed significant antibacterial and antifungal activities. In particular, compounds 3c and 3e showed interesting activities as antibacterial agents while compounds 3a 3c, 3e, 3g, and 3i showed high antifungal activities.     

A Simple,Efficient One‐Pot Synthesis of 2‐Isoxazoline Derivatives and their Antimicrobial Activity

Synthesis of substituted 2‐isoxazolines derivatives with sulfone functional groups was accomplished by 1,3‐dipolar cycloaddition reaction. The 1,3‐dipolar nitrile oxides generated in situ by reacting α‐formaldoximes with N‐bromosuccinimide in the presence of triethylamine on reaction with activated alkenes in toluene at room temperature afford the corresponding 2‐isoxazolines in high yields. All the 2‐isoxazoline derivatives were assayed for their antibacterial activities against Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Pseudomonas aeruginosa and antifungal activities against Aspergillus niger and Candida albicans. Most of the compounds showed good antibacterial and antifungal activities.     

Synthesis and Biological Screening of 2‐Substituted 5,6‐Dihydro‐5‐oxo‐ 4H‐1,3,4‐oxadiazine‐4‐propanenitriles and of Their Intermediates

To evaluate the effect of substituents on biological activities of electron‐rich N‐containing heterocycles, the variably 2‐substituted 5,6‐dihydro‐5‐oxo‐4H‐1,3,4‐oxadiazine‐4‐propanenitriles 26 – 33 were synthesized and evaluated for antibacterial, antifungal, and enzyme‐inhibition activities. The target compounds were obtained from alkyl 4‐ or 3‐hydroxy benzoates 1 and 2 , respectively, and from methyl indoleacetate 3 . The phenolic OH group of benzoates 1 and 2 were substituted with p‐toluenesulfonyl (→ 4 and 5 ), benzoyl (→ 6 and 7 ), and benzyl groups (→ 8 and 9 ) and then converted to 5,6‐dihydro‐5‐oxo‐4H‐1,3,4‐oxadiazine‐4‐propanenitriles. To establish structure‐activity relationships (SAR), a pharmacological screening of the intervening intermediates was also conducted, which revealed that the intermediate hydrazide 11 possesses significant antimicrobial and MAO‐A inhibiting properties and intermediates 12, 24, 28 , and 29 appreciable antifungal activities. Compound 7 inhibits α‐chymotrypsin.     

Cyanoacetamide Intermediate in Heterocyclic Synthesis: Synthesis and Biological Evaluation of Hitherto New Dioxoisoindoline Heterocyclic Derivatives

Innovative poly‐substituted heterocyclic rings incorporating dioxoisoindoline ( 2 – 25 ) were synthesized through the reaction of dioxoisoindoline derivative 2 as starting compound with various types of reagents. All compounds were characterized by appropriate means of (¹H‐NMR, ¹³C‐NMR, IR, and mass). The prepared compounds were evaluated as antimicrobial agents against Escherichia coli, Staphylococcus aureus, and Candida albicans microorganisms. The tested compounds exhibited low to moderate antibacterial activities and promising results as antifungal agents.     

Arylthio analogs of 5,8-quinolinedione: Synthesis,characterization, antibacterial,and antifungal evaluations

Abstract

A set of bis(arylthio) substituted 5,8-quinolinedione derivatives were synthesized and investigated for their in vitro antimicrobial effect. The antibacterial and antifungal activities of 6,7-bis(arylthio)-5,8-quinolinedione (4a–f) and 6,7-bis(arylthio)-2-methyl-5,8-quinolinedione (5a–f) were evaluated against four gram-negative bacteria, three gram-positive bacteria, and three fungi strains. The bis(methoxyarylthio) 5,8-quinolinedione analogs presented better activity against especially gram-positive bacteria compared to bis(halogenarylthio) 5,8-quinolinedione analogs. Bis(3-methoxyarylthio) 5,8-quinolinedione (4e) had the same activity of the reference drug against Staphylococcus aureus. Bis(2-methoxyarylthio) 5,8-quinolinedione (4f) showed two-and-a half-fold better activity with 89.69?μM against Enterococcus faecalis, and two-fold better activity with 11.20?μM against Staphylococcus epidermidis. Bis(2-methoxyarylthio)-2-methyl-5,8-quinolinedione 5f exhibited five-fold higher antibacterial activity with 43.44?μM against E. faecalis and also eight-fold activity of the reference drug with 2.71?μM against S. epidermidis.     

Metal‐based isatin‐bearing sulfonamides: their synthesis,characterization and biological properties

A new series of antibacterial and antifungal isatin bearing sulfonamides and their cobalt (II), copper (II), nickel (II) and zinc (II) metal complexes have been synthesized, characterized and screened for their in vitro antibacterial activity against Bacillus cereus, Corynebacterium diphtheriae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Salmonella typhi, Shigilla dysentriae and Staphylococcus aureus and for in vitro antifungal activity against Trichophyton schoenleinii, Candid glabrata, Pseudallescheria boydii, Candida albicans, Aspergillus niger, Microsporum canis and Trichophyton mentagrophytes. The results of these studies revealed that all compounds showed moderate to significant antibacterial activity. The brine shrimp bioassay was also carried out to study their in vitro cytotoxic properties. Only three compounds, 2, 11 and 22 displayed potent cytotoxic activity as LD₅₀ = 1.56 × 10^?7, 1.59 × 10^?7 and 1.67 × 10^?7 M /ml respectively, against Artemia salina. Copyright © 2006 John Wiley & Sons, Ltd.     

Synthesis and biological activities of benzothiazole derivatives bearing a 1,3,4-thiadiazole moiety

A series of benzothiazole derivatives bearing a 1,3,4-thiadiazole moiety were designed, synthesized and evaluated for their antibacterial, antifungal and antiviral activities. The bioassay results indicated that most of target compounds showed good antiviral activities against tobacco mosaic virus (TMV) and antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo) and Ralstonia solanacearum (Rs). Especially, the anti-Xoo effect of title compounds 5k (N-(5-methoxybenzo[d]thiazol-2-yl)-2-((5-(2-tolyl)-1,3,4-thiadiazol-2-yl)thio)acetamide) and the anti-Rs effect of title compounds 5a (N-(5-nitrobenzo[d]thiazol-2-yl)-2-((5-(4-(trifluorom ethyl)phenyl)-1,3,4-thiadiazol-2-yl)thio)acetmide) respectively reached 52.4% and 71.6% at 100?µg/mL, which are superior to that of bismerthiazol (32.0% and 52.3%). In addition, the protective and inactivation activities of title compound 5i (N-(5-methoxybenzo [d]thiazol-2-yl)-2-((5-(4-nitrophenyl)-1,3,4-thiadiazol-2-yl)thio)acetamide) against TMV were 79.5% and 88.3%, respectively, which are better than that of ningnanmycin (76.4% and 86.8%). The above research showed that benzothiazole derivatives bearing a 1,3,4-thiadiazole moiety may be used as potential molecular templates in searching for highly-efficient antiviral and antibacterial agents.     

Anthraquinones from the Aerial Parts of Rubia cordifolia with Their NO Inhibitory and Antibacterial Activities

The present study aimed to identify the composition of the aerial parts of Rubia cordifolia L. A chemical investigation on the EtOAc extracts from the aerial parts of Rubia cordifolia resulted in the isolation of four new anthraquinones, namely Cordifoquinone A–D (1–4), along with 16 known anthraquinones. Their structures were elucidated on the basis of NMR and HR-ESIMS data. All isolates were assessed for their inhibitory effects on NO production in LPS-stimulated RAW 264.7 macrophage cells. Compounds 1, 3 and 10 exhibited significant inhibitory activities with IC₅₀ values of 14.05, 23.48 and 29.23 μmol·L⁻¹, respectively. Their antibacterial activities of four bacteria, Escherichia coli (ATCC 25922), Staphylococcus aureus subsp. aureus (ATCC 29213), Salmonella enterica subsp. enterica (ATCC 14028) and Pseudomonas aeruginosa (ATCC 27853), were also evaluated. Our results indicated that the antibacterial activity of these compounds is inactive.