Microwave-Assisted Synthesis of 2-Long Alkenyl Chain Benzoxazoles and Naphtho[2,3-d]oxazoles and Their Antimicrobial Evaluation

A microwave-assisted combinatorial synthesis of 2-long alkenyl chain benzoxazoles and naphtho[2,3-d]oxazoles with a catalytic amount of phosphorus pentasulphide at ambient pressure has been developed. This procedure constitutes a simple, practical, and green synthetic method for benzoxazoles and their structural analogs. All the compounds [2(a–d) through 6(a–d)] have been screened for antibacterial and antifungal activity. The compounds have showed good activity against Gram-positive and Gram-negative bacteria. All the compounds have also showed good results against almost all fungal strains. The structures of the synthesized compounds are elucidated by IR, ¹H NMR, ¹³C NMR, MS data, and elemental analysis.     

Advancements in the Synthesis and Applications of Cationic N‐Heterocycles through Transition Metal‐Catalyzed C−H Activation

Cationic N‐heterocycles are an important class of organic compounds largely present in natural and bioactive molecules. They are widely used as fluorescent dyes for biological studies, as well as in spectroscopic and microscopic methods. These compounds are key intermediates in many natural and pharmaceutical syntheses. They are also a potential candidate for organic light‐emitting diodes (OLEDs). Because of these useful applications, the development of new methods for the synthesis of cationic N‐heterocycles has received a lot of attention. In particular, many C?H activation methodologies that realize high step‐ and atom‐economies toward these compounds have been developed. In this review, recent advancements in the synthesis and applications of cationic N‐heterocycles through C?H activation reactions are summarized. The new C?H activation reactions described in this review are preferred over their classical analogs.     

Synthesis and Antimicrobial Evaluation of Novel Dibenzo‐18‐Crown‐6‐Ether Functionalized Pyrimidines

A practical, two‐step synthesis of crown ether functionalized pyrimidines has been developed. The reaction conditions have been optimized, and the protocol is generalized for series of substrates. These newly synthesized compounds exhibited antimicrobial activity against bacterial strains Staphylcoccus aureus (Gram‐positive) and Escherichia coli (Gram‐negative). These compounds were also found to be potent antifungal agents Aspergillus niger and Candida albicans strains, respectively.     

Synthesis and evaluation of some new 5-(hetaryl)thiazoles as potential antimicrobial agents

In continuing our efforts to find new effective antimicrobial agents for overcoming the problem of microbial resistance, a new series of functionalized 5-hetarylthiazoles have been designed and synthesized starting from readily accessible 1-(2-allylamino-4-methylthiazol-5-yl)ethanone (3). The structures of newly synthesized compounds were confirmed by elemental analyses, spectral data, and chemical transformations. The synthesized compounds were evaluated in vitro for their antimicrobial activity against some human pathogenic bacterial and fungal strains. The compounds 7, 18, and 24 exhibited higher antibacterial activity with minimum inhibitory concentration (MIC) values ranging from (0.03–0.06?µg/mL) than ampicillin (MIC, 0.12?µg/mL) against Streptococcus pneumoniae. Whereas compounds 4, 22, and 24 revealed higher antifungal potency than amphotericin B against Aspergillus fumigatus. The structure and antimicrobial activity relationship was also discussed.     

Synthesis and cytotoxic activity of heterocyclization products of 1,1-dicyano-2-hetaryl-2-trifluoromethylethylenes

Methods for the synthesis of novel fluorinated compounds by reaction of 1,1-dicyano-2-hetaryl-2-trifluoromethylethylenes with a variety of nitrogen heterocycles have been developed. Cyctotoxicity of the obtained organofluorine heterocycles were studied in vitro at the U.S. National Cancer Institute (NCI) in the framework of the International Program for Development of Effective Antitumor Drugs. Cytotoxic activity in the series of fluorinated pyrazolo[1,5-a]pyrimidines has been observed for the first time, this strongly depending on the nature and position of the substituents.     

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.     

Studies on Antimicrobial Evaluation of Some 1-((1-(1H-Benzo[d]imidazol-2-yl)ethylidene)amino)-6-((arylidene)amino)-2-oxo-4-phenyl-1, 2-dihydropyridine-3,5-dicarbonitriles

A new series of 1-((1-(1H-benzo[d]imidazol-2-yl)ethylidene)amino)-6-((arylidene)amino)-2-oxo-4-phenyl-1,2-dihydropyridine-3,5-dicarbonitriles (4a–o) have been synthesized for the development of antimicrobial agents. Newly synthesized compounds were evaluated for their in vitro antibacterial activity against Gram-positive bacteria (Pseudomonas aeruginosa, Streptococcus pyogenes), Gram-negative bacteria (Escherichia coli, Staphylococcus aureus), and antifungal activity (Candida albicans, Aspergillus niger, Aspergillus clavatus). These compounds were characterized by infrared, ¹H NMR, ¹³C NMR, and mass spectra. The synthesized compounds 4b, 4e, 4 h, and 4k showed potent antimicrobial activity against tested microorganisms.     

Urea and thiourea derivatives of 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1, 2, 4]triazolo[4,3-a]pyrazine: Synthesis,characterization, antimicrobial activity and docking studies

Abstract

An efficient and robust synthetic procedure was developed primarily for the synthesis of a precursor compound; 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1, 2, 4]triazolo[4,3-a]pyrazine (11), from 2-chloropyrazine (7) through the chemical transformations such as hydrazine substitution, trifluoroacetyl group induction, cyclization and pyrazine ring reduction. A new series of urea derivatives 13a-e and thiourea derivatives 13f-j of compound 11 have been synthesized and the structures of all the compounds were confirmed using spectroscopic analyses such as IR, ¹H NMR, ¹³C NMR, LC-MS and HRMS. The newly synthesized compounds were screened for their in vitro antimicrobial activity against five bacteria and two fungi, in which compounds 13d, 13i and 13j displayed potential activity against bacterial strains and 13a, 13d, 13g and 13j against fungal strains with the MIC values in the range of 6.25–25.0 µg/mL. An overall comparison of the activity results revealed that thiourea derivatives contain better activity than that of urea compounds. Molecular docking studies on poly (ADP-ribose) polymerase 15 (ARTD7, BAL3) demonstrated that all the synthesized compounds possess significant binding energies (-8.1 to -9.8?kcal/mol) with no adverse effect in the active site of protein.     

Synthetic routes to seven and higher membered S-heterocycles by use of metal and nonmetal catalyzed reactions

Nitrogen, oxygen, and sulfur containing heterocycles have a wide range of biological activities. Metal and nonmetal catalysts are used in organic reactions with high activity. New strategies have been developed for the preparation of heterocycles in the last decades. The metal and nonmetal catalyzed synthesis of heterocycles is becoming an important and highly rewarding protocol in organic synthesis. In this review article, the synthesis of seven and higher-membered S-heterocycles is presented with the application of metal and nonmetal catalysts for the period from 1968 to 2018.     

Synthesis of pyrazolo-enaminones,bipyrazoles and pyrazolopyrimidines and evaluation of antioxidant and antimicrobial properties

A novel pyrazolo-enaminones, bipyrazoles and bipyrazolopyridines from 1-(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)butane-1,3-dione and 4-methyl-2-phenyl-2H-pyrazolo[3,4-b]pyridine-3,6(3aH,7H)-dione have been synthesized by assisted heating with microwave radiation without any catalyst. The pyridine and pyrazole ring formation has been developed from easily accessible enamino keto esters by formylation followed by intramolecular cyclization. The general applicability for the synthesis of the important pyrazolo-enaminones, bipyrazoles and pyrazolo-pyridines heterocycles was attributed to simplicity of operation, synthesis without catalyst, energy efficiency (shorter reaction time under microwave irradiation), good yields, more environmentally friendly and more cost-effective procedure. The antioxidant activity of new heterocyclic compounds was evaluated by free radical scavenging by DPPH assay. Several of these compounds showed good activity against both Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria.     

Facile synthesis,characterization, and antimicrobial studies of some disubstituted 1,2,3-triazoles with sulfonamide functionality

An expedient synthesis of some 1,4-disubstituted 1,2,3-triazoles (3a–3x) having sulfonamide functionality from various terminal alkynes and aromatic azides through Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition has been reported. The structures of newly synthesized compounds were confirmed by IR, ¹H NMR, ¹³C NMR, high-resolution mass spectra and screened for in vitro antimicrobial activity against Staphylococcus aureus (Gram-positive bacteria), Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes (Gram-negative bacteria), Candida albicans, and Aspergillus niger (fungi). Some of the synthesized compounds were found to exhibit good potency against above-tested microbial strains. Moreover, to study the binding interactions, docking simulation of broadly active compound 3x was also performed against E. coli dihydropteroate synthase enzyme.     

Synthesis of 7-Amino-1-nitro-2-heptanone Derivatives

Abstract

New N-substituted 7-amino-1-nitro-2-heptanone derivatives have been obtained starting from readily accessible 2-(nitromethylidene)hexahydro-1H-azepine. These compounds have been further used as starting materials for the synthesis of some heterocycles with 5-aminopentyl fragment.     

Diversity-oriented TsOH catalysis-enabled construction of tanshinone-substituted bis(indolyl/pyrrolyl)methanes and their biological evaluation for anticancer activities

We have developed an efficient and straightforward methodology for the synthesis of novel tanshinone-substituted bis(indolyl/pyrrolyl)methane scaffolds 3 through TsOH catalysis-enabled addition of indoles or pyrroles 1 with tanshinones 2 based on molecular hybridization strategy. Products were smoothly obtained in good yields (up to 81% yield). This protocol also represents the first construction of tanshinone skeleton-fused bis(indolyl/pyrrolyl)methane scaffolds, thus leading to new knowledge in the fields of both molecular complexity and diversity-oriented synthesis and the lead compound discovery. Furthermore, their biological activities against human leukemia cells K562, human prostate cancer cells PC-3, and human lung cancer cells A549 have been preliminarily demonstrated by in vitro assays. The results demonstrated that most of these compounds 3 obtained by this protocol showed comparable activity to the positive control of cisplatin.     

Synthesis and Antimicrobial Studies of Selenadiazolo Benzimidazoles

An efficient and eco‐friendly method has been developed for the synthesis of selenadiazolo benzimidazoles by the condensation of N‐benzylbenzo[c][1,2,5]selenadiazole‐4,5‐diamine with various aromatic aldehydes catalyzed by xanthan sulfuric acid. All the synthesized compounds 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j were evaluated for in vitro antibacterial activity against Gram‐positive bacterial strains (Bacillus subtilis, Staphylococcus aureus, and Streptococcus pyogenes), and Gram‐negative bacterial strains (Escherichia coli, Klebsiella pneumonia, and Salmonella typhimurium) and antifungal against Aspergillus niger, Candida albicans, and Aspergillus flavus (Fungi). Compound 5i emerged as the most interesting compound in this series exhibiting excellent antimicrobial activity.     

Antibacterial and antifungal ferrocene incorporated dithiothione and dithioketone compounds

Two antibacterial and antifungal ferrocene incorporated compounds have been synthesized, characterized and screened for their in vitro antibacterial activity against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Salmonella typhi, Shigella dysenteriae, Bacillus cereus, Corynebacterium diphtheriae, Staphylococcus aureus and Streptococcus pyogenes bacterial strains and for in vitro antifungal activity against Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glaberata. Results show that these compounds have significant activity against tested bacterial and fungal strains and thus introduce a novel class of ferrocene incorporating antibacterial and antifungal compounds. Copyright © 2005 John Wiley & Sons, Ltd.     

In vitro pharmacological screening of three newly synthesised pyrimidine derivatives

The antibacterial and antifungal activities of three new pyrimidine derivatives, namely, 2,6-bis(4,6-dimethylpyrimidin-2-ylthio)benzene-1,4-diol (1),3,5-bis(4,6-dimethylpyrimidin-2-ylthio)-2-methylbenzene-1,4-diol (2) and 3,5-bis(4,6-dimethylpyrimidin-2-ylthio)-2-methoxybenzene-1,4-diol (3), synthesised by electrochemical method are presented here. The compounds were screened for their activities against Gram-positive and Gram-negative bacteria, Bacillus subtilis, Staphylococcusaureus, Escherichia coli and a pathogenic fungus Aspergillus niger. The results show that these compounds have significant activity against these bacteria and fungus. The minimum inhibitory concentration of compound 1 was determined as 62.5 μg/mL against B. subtilis, 125 μg/mL against E. coli and 250 μg/mL against S. aureus establishing its promising activities higher than susceptible ranges.     

N'-(1-([1,1'-biphenyl]-4-yl)ethylidene)-2-cyanoacetohydrazide as scaffold for the synthesis of diverse heterocyclic compounds as prospective antitumor and antimicrobial activities

In this article, the main target was to study the antitumor and antimicrobial efficacy of new heterocycles conjugated with biphenyl moiety in-vitro. This was implemented by utilizing N'-(1-([1,1'-biphenyl]-4-yl)ethylidene)-2-cyanoacetohydrazide 3 as a material for the synthesis of various heterocyclic compounds. Among of them, some compounds were selected and assayed against two antitumor cell lines as (HepG2) and (HCT-116). Conspicuously, the achieved results showed that compounds 6, 13, and 23 possess significant potency against both cancer cell lines. Particularly, compound 13 exhibited a remarkable efficacy, similar to the standard anticancer drug (doxorubicin), against both cancer cell lines. Noteworthy, compound 13 may serve as a potential anticancer therapeutic drug in the future. On the other hand, In-vitro antifungal and antibacterial activities of selected compounds were assayed and the results indicated that the compound 6 exhibited significant potency against Candida albicans, while compounds 6 and 8 displayed spectacular results for the antibacterial study.     

Synthetic modifications in ethyl 2-amino-4-methylthiazole-5-carboxylate: 3D QSAR analysis and antimicrobial study

Ethyl 2-amino-4-methylthiazole-5-carboxylate (1) is a very substantial derivative of the thiazole group. This derivative has been modified and has been synthesized using readily available materials. The structures of synthesized derivatives were confirmed by IR, ¹H NMR, ¹³C NMR, and mass spectral techniques. The newly prepared compounds (5a–k) were studied for their antimicrobial activities against strains of bacteria (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pyogenes) and fungi (Candida albicans, Aspergillus niger, and Aspergillus clavatus) using serial dilution method. Structure-activity relationship was carried out by CoMFA and CoMSIA with the help of 3D-QSAR analysis. As per the database alignment, the CoMFA and CoMSIA models were developed. Information based on these models is useful for structure-activity relationships of the reported molecules.     

Cobalt-catalyzed C–N,C–O,C–S bond formation: synthesis of heterocycles

In recent decades, a large number of reports related to the synthesis of N-, O- and S-containing heterocycles have appeared owing to a wide variety of their biological activity. Traditional approaches require expensive or highly specialized equipment or would be of limited use to the synthetic organic chemist due to their highly inconvenient approaches. New strategies have been developed for the preparation of heterocycles in the last decades. Metal and non-metal catalysts are used in organic reactions with high activity. These synthetic strategies are becoming important and highly rewarding protocols in organic synthesis. In this review article, the synthesis of heterocycles is presented with the application of cobalt metal as a catalyst. It describes the formation of different sized heterocyclic rings containing different heteroatoms.

     

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.