5-Nitroimidazole derivatives as possible antibacterial and antifungal agents

Some novel 1-[2-[[5-(2-furanyl)-4-substituted 4H-1,2,4-triazol-3-yl[thio[ethyl[-2-methyl-5-nitro-1H-imidazoles (3), 1-[3-[[5-(2-furanyl/2-thienyl)-4-substituted 4H-1,2,4-triazol-3-yl[-thio]-2-hydroxypropyl[-2-methyl-5-nitro-1H- imidazoles (5) and 1-[3-[(N,N-disubstituted thiocarbamoyl)-thio[-2-hydroxypropyl]-2-methyl-5-nitro-1H-imidazoles (7) were synthesized and evaluated for in vitro antibacterial and antifungal activity. Some of 5 were found to be effective against bacteria and fungi (minimum inhibitory concentration (MIC) 7.3-125 micrograms/ml), whereas 7 were found to be effective against fungi (MIC 3-25 micrograms/ml).     

Research on antibacterial and antifungal agents. III. Synthesis and antimicrobial activity of 2-methyl-5-aryl-3-furoic acids and 2-methyl-3-imidazolylmethyl-5-aryl furans

The synthesis and microbiological activities of 2-methyl-5-aryl-3-furoic acids and 2-methyl-3-imidazolyl-methyl-5-aryl-3-furans are reported. Antimicrobial data in comparison with pyrrolnitrin showed an interesting antifungal activity but a very poor antibacterial activity. The presence of an imidazole nucleus does not increase antifungal activity. The introduction of a substituent in the para position of the aryl at a C5 of the furan ring affects antifungal activity.     

Evaluation of some classical hydrazones of ketones and 1,2-diketones as antileishmanial, antibacterial and antifungal agents

The paper describes the synthesis and antimicrobial (antileishmanial, antibacterial and antifungal) activity of some classical hydrazones of benzophenones and of 1,2-diketones. N-(Diaryl) acyl derivatives of these hydrazones have also been synthesized and evaluated. 4,4,-Demthoxybenzil monohydrazone and 4,4'-dimethoxybenzophenone hydrazone showed significant antileishmanial activity. The effect of substituents on the bioactivity is discussed.     

Synthesis and characterization of new types of 2-(6-methoxy-2-naphthyl)propionamide derivatives as potential antibacterial and antifungal agents

A series of novel 2-(6-methoxy-2-naphthyl)propionamide derivatives have been efficiently synthesized in excellent yields via the reaction of naproxenoyl chloride with different amino compounds. Most of the synthesized compounds were screened in vitro for their antibacterial and antifungal activities. Most of the compounds showed significant antibacterial and antifungal activities, reaching, in certain cases, the same level of antimicrobial activity as the standard antibacterial agent Ampicilline and antifungal agent Flucanazole. N-(4-(N-arylsulfamoyl)phenyl)-2-(6-methoxynaphthalen-2-yl)propanamide (4a–c), 4-(4-fluorobenzylidene)-2-(1-(6-methoxynaphthalen-2-yl)ethyl)oxazol-5(4H)-one (10b), 2-(6-methoxynaphthalen-2-yl)-N-((5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl)propanamide (12), and N-((4-amino-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl)-2-(6-methoxynaphthalen-2-yl)propanamide (13) were found to be the most potent compounds against most of the tested strains. The antimicrobial activity was further supported by using MIC technique. Structure activity relationship studies revealed several matching pairs.     

The synthesis and potassium channel blocking activity of some (4-methanesulfonamidophenoxy)propanolamines as potential class III antiarrhythmic agents

The synthesis of 22 (4-methanesulfonamidophenoxy)propanolamines and their testing on isolated guinea pig cardiac myocytes, on isolated preparations from guinea pig atria, and on rat blood pressure are described. Secondary amines in the series (11a-f) showed residual beta-blocking activity, whereas incorporation of N-methyl phenylalkyl and 4-phenyl alicyclic amine groups abolished beta-blocking activity but led to enhanced ability to block the channel conducting the delayed rectified potassium current, and hence produced an increase in the cardiac action potential duration (APD). Incorporation of hydrophobic Cl and CF3 groups further enhanced potassium channel blocking activity. Compounds 81 and 8m produced a significant increase in APD at nanomolar concentrations, with no effect on cardiac muscle conduction velocity, and hence merit further investigation as Class III antiarrhythmic agents. Methylation of the methanesulfonamido group abolished channel-blocking activity; 4-carboxy and 3-methanesulfonamido analogues retained activity but at a reduced level.     

Recyclable CuO nanoparticles-catalyzed synthesis of novel-2,5-disubstituted 1,3,4-oxadiazoles as antiproliferative,antibacterial, and antifungal agents

A series of new 2,5-disubstituted 1,3,4-oxadiazoles have been conveniently synthesized through an oxidative C–O coupling by direct C–H bond activation of N-aroyl-N-arylidinehydrazines using a catalytic quantity of CuO nanoparticles. Twenty compounds have been synthesized in good to excellent yields (75–90 %). All the synthesized compounds were evaluated for their in vitro antiproliferative, antibacterial, and antifungal activity. Compounds 8d and 10d are more promising antiproliferative agents with IC₅₀ value of 3.66 and 3.89 µM in MCF-7 cell line, and compounds 8a and 10a were showed more potent antifungal activity than standard drug.     

Microwave-assisted synthesis of some novel and potent antibacterial and antifungal compounds with biological screening

Hydantoins have widely been used as antiarrythmic, anticonvulsant and antitumor agents but recent research has shown a different and novel cytotoxic activity of hydantoins and its derivatives, i.e. anti HIV, antibacterial and antifungal. The following research article deals with the synthesis of hydantoins and their derivatives by Mannich reaction viz., 3-(substituted)-5,5-diphenylimidazolidine-2,4-dione and 1-(substituted)-3,5,5-triphenylimidazolidine-2,4-dione. The synthesised compounds are novel and some of the compounds showed good antibacterial and antifungal activity equivalent to the standards used. All synthetic procedures were carried out in a microwave and not by conventional methods, which led to speedy process and high yield for the same.     

Synthesis of some novel 2-substituted benzoxazoles as anticancer, antifungal, and antimicrobial agents

Benzoxazole derivatives show various types of biological properties such as antiviral, antineoplastic, anti-HIV-1, antitubercular, anthelmintic, antimicrobial, and antifungal activities. In the last few years 2-substituted benzoxazole derivatives have been studied extensively for their antitumor, antiviral, and antimicrobial activities. In an effort to identify new candidates that may be of value in designing new, potent, selective, and less toxic anticancer, antiviral, and/or antimicrobial agents, we synthesized 2-[(arylhydrazono) cyanomethyl]-5-chloro benzoxazoles (II), 2-[(arylidene)cyanomethyl]-5-halo benzoxazoles (III), and 2-[(cycloalkylidine)cyanomethyl]-5-chlorobenzoxazoles (IV), and tested them for anticancer, antifungal, and antibacterial activities. Some of these (compounds 11, 14) were found to possess anticancer activity and remarkable antifungal as well as antibacterial activities.     

Phospho-MurNAc-pentapeptide translocase (MraY) as a target for antibacterial agents and antibacterial proteins

Phospho-MurNAc-pentapeptide translocase (MraY, translocase I) catalyses the first step of the lipid-linked cycle of reactions of bacterial peptidoglycan biosynthesis. MraY is the target for five families of nucleoside antibacterial natural products: the tunicamycins, the mureidomycins (also pacidamycins, napsamycins), the liposidomycins, the muraymycins, and the capuramycins. Recent structure-activity studies on these families have led to the identification of active pharmacophores, and insight into their mechanisms of action. This step of peptidoglycan biosynthesis is also the target for the bacteriolytic E protein from bacteriophage phiX174, and for cyclic peptides of the amphomycin family which complex the undecaprenyl phosphate co-substrate. The mechanisms of enzyme inhibition by these agents are discussed, and the state of knowledge regarding the transmembrane structure, active site, and catalytic mechanism of MraY. The availability of high throughput assays and prospects of MraY as an antibacterial target are also discussed.     

Gold(III) complexes as potential antitumor agents: solution chemistry and cytotoxic properties of some selected gold(III) compounds

Gold(III) complexes generally exhibit interesting cytotoxic and antitumor properties, but until now, their development has been heavily hampered by their poor stability under physiological conditions. To enhance the stability of the gold(III) center, we prepared a number of gold(III) complexes with multidentate ligands - namely [Au(en)(2)]Cl(3), [Au(dien)Cl]Cl(2), [Au(cyclam)](ClO(4))(2)Cl, [Au(terpy)Cl]Cl(2), and [Au(phen)Cl(2)]Cl - and analyzed their behavior in solution. The solution properties of these complexes were monitored by visible absorption spectroscopy, mass spectrometry, and chloride-selective potentiometric measurements; the electrochemical properties were also studied by cyclic voltammetry and coulometry. Since all the investigated compounds exhibited sufficient stability under physiological conditions, their cytotoxic properties were tested in vitro, via the sulforhodamine B assay, on the representative human ovarian tumor cell line A2780, either sensitive or resistant to cisplatin. In most cases the investigated compounds showed relevant cell-killing properties with IC(50) values falling in the 0.2-10 microM range; noticeably most investigated gold(III) complexes were able to overcome, to a large extent, resistance to cisplatin when tested on the corresponding cisplatin-resistant cell line. The cytotoxic properties of the free ligands were also determined under the same solution conditions. Ethylenediamine, diethylenetriamine, and cyclam were virtually nontoxic (IC(50) values > 100 microM) so that the relevant cytotoxic effects observed for [Au(en)(2)]Cl(3) and [Au(dien)Cl]Cl(2) could be quite unambiguously ascribed to the presence of the gold(III) center. In contrast the phenanthroline and terpyridine ligands turned out to be even more cytotoxic than the corresponding gold(III) complexes rendering the interpretation of the cytotoxicity profiles of the latter complexes less straightforward. The implications of the present findings for the development of novel gold(III) complexes as possible cytotoxic and antitumor drugs are discussed.     

Complexes of ruthenium(III) with some 2-aminothiazole derivatives/synthesis, properties and pharmacological studies

Four new complexes of Ru(III) with a general formula [Ru(L)2Cl2]Cl, where L = 2-amino-4-phenylthiazole (CAS 2010-06-2), 2-amino-4-methylthiazole (CAS 1603-91-4), ethyl 2-amino-4-methyl-5-thiazolecarboxylate (CAS 7210-76-6) and ethyl 2-amino-4-phenyl-5-thiazolecarboxylate (CAS 64399-23-1), were prepared. The syntheses were carried out in polar medium and inert atmosphere at a molar ratio Ru:L = 1:2 or 1:3. The compounds obtained were characterised by IR-, 1H-NMR- 13C-NMR-, UV-VIS-, EPR spectroscopy, magnetochemical and conductivity measurements. The ligands behaved as bidental, bounding Ru(III) through the nitrogen atoms from the amino group and the heterocycle. The complex of ethyl 2-amino-4-phenyl-5-thiazolecarboxylate showed significant antileukaemic activity on various human cells (IC50 values ranging from 20 to 92 micromol/l). Toxicological studies on mice indicated that such concentrations could be reached without mortality. This compound exhibited a promising antineoplastic potential and needs further pharmacological and toxicological evaluation.     

Synthesis and evaluation of some new fluorinated hydroquinazoline derivatives as antifungal agents

The key intermediate octahydroquinazoline (1) was obtained in one pot synthesis by a modification of the Biginelli reaction. Compound 1 was allowed to react with phenacyl bromide and bromomalononitrile to furnish thiazolo[2,3-b]quinazoline 3 and 12, respectively. Interaction of compound 12 with formamide, formic acid and phenyl isothiocyanate yielded the corresponding pyrimidino[4',5':4.5]thiazolo[2,3-b] quinazolines 13, 14 and 17, respectively. The structure of the synthesized compounds were elucidated by elemental analyses and spectroscopic analyses. Some of the prepared compounds were tested for their antifungal activity in comparison with tioconazole as a reference fungicide.     

Mild and highly efficient copper (II) sulfate catalyzed one pot synthesis of 2-aryl benzimidazole using atmospheric air as an oxidant and its antibacterial study

A simple, efficient, and environmentally benign method has been developed for the synthesis of 2-substituted benzimidazole using one pot reaction of o-phenylenediamine with substituted aldehydes in good to excellent yields under mild conditions using low catalyst loading (CuSO₄ as the selective catalyst) and atmospheric air as an oxidant. All synthesized compounds were evaluated for their in vitro anti bacterial activity against six microorganisms: Staphylococcus aureus (ATCC 11632), Streptococcus feacalis (clinically isolated), Bacillus cerus (MTCC 7350), Escherichia coli (ATCC 35218), Salmonella typhi (ATCC15499), and Pseudomonas aeruginosa (ATCC 23564). It was observed that all compounds exhibited good to moderate activity as compared to standard drug. The easy setup and purification procedure of this sustainable method and biological importance makes it appealing for bulk industry applications.     

Synthesis and antibacterial and antifungal activity of some new pyrimidin-2(5H)-one/thione and 4H-chromen-4-one derivatives

A new synthesis of 2-substituted-4H-chromen-4-ones (IVa-c) and 4-(2-hydroxyphenyl)-6-substituted pyrimidin-2(5H)-one/thiones (Va – Vc)/(VIa – VIc) derivatives is reported. First, benzoyloxy esters are converted into their 1,3-diones (IIIa – IIIc) by using dry KOH in pyridine via the Baker – Venkataraman transformation reaction. Then, 1,3-diones thus obtained are cyclised into 2-substituted-4H-chromen-4-ones (IVa – IVc) and 4-(2-hydroxyphenyl)-6-substituted pyrimidin-2(5H)-one/thiones (Va – Vc)/(VIa – VIc) by refluxing in acetic acid and urea/thiourea in ethanol, respectively. The newly synthesized compounds were characterized by IR, ¹H NMR, and mass spectroscopy and elemental analysis and tested for their antibacterial and antifungal activity.     

Indole/isatin-containing hybrids as potential antibacterial agents

The emergence and worldwide spread of drug-resistant bacteria have already posed a serious threat to human life, creating the urgent need to develop potent and novel antibacterial drug candidates with high efficacy. Indole and isatin (indole-2,3-dione) present a wide structural and mechanistic diversity, so their derivatives possess various pharmacological properties and occupy a salient place in the development of new drugs. Indole/isatin-containing hybrids, which demonstrate a promising activity against a panel of clinically important Gram-positive and Gram-negative bacteria, are privileged scaffolds for the discovery of novel antibacterial candidates. This review, covering articles published between January 2015 and May 2020, focuses on the development and structure–activity relationship (SAR) of indole/isatin-containing hybrids with potential application for fighting bacterial infections, to facilitate further rational design of novel drug candidates.     

Research on antibacterial and antifungal agents. VII. Synthesis of (1-pyrryl)methylquinolines acids

Some (1-pyrryl)methyl derivatives of 1-ethyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid were synthetized by the standard procedure involving Gould-Jacobs and Lappin reactions. The above derivatives were tested microbiologically as nalidixic acid analogs and compared with some clinically useful 4-oxopyridine-3-carboxylic acids (nalidixic acid, pipemidic acid, norfloxacin, enoxacin and ciprofloxacin). Their antibacterial activities were very weak.     

2-Acetylpyridine thiosemicarbazones XI: 2-(alpha-Hydroxyacetyl)pyridine thiosemicarbazones as antimalarial and antibacterial agents

A series of 2-(alpha-hydroxyacetyl)pyridine thiosemicarbazones was synthesized as potential antimalarial and antibacterial agents. Their synthesis was achieved by the condensation of N4-mono- or N4,N4-disubstituted thiosemicarbazides with 2-(alpha-hydroxyacetyl)pyridine. The latter was prepared by selective bromine oxidation of (2-pyridinyl)-1,2-ethanediol. The new compounds show potent inhibitory activity against penicillin-sensitive as well as penicillin-resistant Neisseria gonorrhoeae (MIC, 0.5-0.004 micrograms/mL), against Neisseria meningitidis (MIC, 0.5-0.032 micrograms/mL), and Staphylococcus aureus (MIC, 0.5-2 micrograms/mL). Good in vitro antimalarial effects against Plasmodium falciparum (Smith strain; ID50, 6.7-38 ng/mL) were observed in most of these new agents, but only 3 of 12 compounds exhibit moderate in vivo activity against Plasmodium berghei. These new agents appear to be less toxic to the host and more water soluble than the corresponding 2-acetylpyridine thiosemicarbazones.