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Candida albicans, as the most prevalent opportunistic pathogenic fungus, has caused great difficulty in its clinical management. At the same time, azole resistance is emerging as their extensive usage in clinical practice. In this case, the adoption of combination therapy has become a promising therapeutic strategy. In this study, a series of deguelin (Deg) derivative were prepared and identified with in vitro antifungal activity against drug-resistant C. albicans combined with fluconazole (FLC). The combination of Deg derivative 17c and FLC exhibited the best activity, with a fractional inhibitory combination index (FICI) of 0.02. The sensitization effect of 17c + FLC was further validated by the temporal fungicidal curve analysis. In addition, 17c + FLC also demonstrated inhibitory effects on the mycelial transformation and biofilm formation of resistant C. albicans, and significantly reduced the expression of key genes related to the RAS1/cAMP/PKA cell-transduction pathway. [ABSTRACT FROM AUTHOR]

Most fungal infections are common, localized to skin or mucosal surfaces and can be treated effectively with topical antifungal agents. However, while invasive fungal infections (IFIs) are uncommon, they are very difficult to control medically, and are associated with high mortality rates. We have previously described highly potent bis-guanidine-containing heteroaryl-linked antifungal agents, and were interested in expanding the range of agents to novel series so as to reduce the degree of aromaticity (with a view to making the compounds more drug-like), and provide broadly active high potency derivatives. We have investigated the replacement of the central aryl ring from our original series by both amide and a bis-amide moieties, and have found particular structure-activity relationships (SAR) for both series', resulting in highly active antifungal agents against both mold and yeast pathogens. In particular, we describe the in vitro antifungal activity, absorption, distribution, metabolism and elimination (ADME) properties, and off-target properties of FC12406 (34), which was selected as a pre-clinical development candidate. [ABSTRACT FROM AUTHOR]

Some new N-substituted hetero aromatic compounds, derived from clotrimazole, were synthesized. In this regard, imidazole ring of clotrimazole was replaced by pyrazole (Series A; P1-P4) and benzimidazole moieties (Series B; P5-P8). All new compounds were evaluated against different species of fungi using broth microdilution method as recommended by clinical and laboratory standard institute (CLSI). Their cytotoxicity was assessed against MRC-5 as normal human fibroblasts cell line using MTT method. To augury the binding mode of the synthesized compounds against cytochrome P450 lanosterol 14α-demethylase, molecular docking studies were also performed. Our results indicated that some compounds showed desirable antifungal activities at concentrations ranging from 0.5 to 1 µg/mL. Among them, compounds 4-nitro-1-trityl-1H-pyrazole (P2) and 5-cyclopropyl-2-trityl-2H-pyrazol-3-ylamine (P4) which bearing pyrazole ring, had the most antifungal activities (MIC50 = 0.25–16 µg/mL), against all tested fungi species. Moreover, compound P4 showed bactericidal activity at higher concentration of MIC. In vitro cytotoxic evaluation revealed that the potent compounds (P2 and P4) were non-toxic at therapeutic dosages toward human cells. In addition, the results showed good correlation between docking energies and biological activities of the compounds. According to both antifungal and computational studies, P4, which containing special chemical structure, had desire potential to be consider as antifungal agent. Also, Density functional theory (DFT) was employed to study the reactivity descriptors of P4 such as HOMO-LUMO energy gap, electronegativity, electron affinity, ionization potential, molecular hardness, and molecular softness. Based on the DFT study, the heterocyclic residue of P4 has the favourable potent in accepting electrophilic reactions which is in agreement with the experimental data. [ABSTRACT FROM AUTHOR]

A series of novel 10-Undecenoic acid-based triazole derivatives were designed and synthesized in the present study. 10-Undecenoic acid on treatment with propargyl bromide yielded the corresponding ester which was reacted with different aryl azides to obtain the novel triazoles. The synthesized compounds were characterized by NMR, IR, and mass spectral data. The synthesized lipidic triazole compounds were studied for the antibacterial and antifungal activities against Ralstonia solanacearum and Fusarium oxysporum, respectively. The antimicrobial assay results revealed that the synthesized compounds possessed a certain degree of antifungal and antibacterial activities on the tested organisms. Among all the compounds, it was found that compounds 4j (with iodo substituent) and 4q (tert-butyl substituent) displayed the highest antibacterial and antifungal activity respectively. The study revealed that novel lipidic triazole derivatives of 10-Undecenoic acid could be potential antimicrobial compounds. This is the first report on the design, synthesis, and antimicrobial assessment of 10-Undecenoic acid-based triazole against plant pathogenic microorganisms. [ABSTRACT FROM AUTHOR]

Some substituted isatins 3a–3c were prepared by Sandmeyer's synthesis from different substituted anilines 1a–1c and transformed into corresponding N-alkyl isatins 4a–4j. These substituted N-alkyl isatins were condensed with N-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)thiosemicarbazide to give new substituted isatin N-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)thiosemicarbazones 6a–6j with different substituents at 1-, 5- and 7- as well as 5,7-positions of isatin ring. The antibacterial as well as antifungal activity of these thiosemicarbazones was estimated using minimum inhibitory concentration protocol. Amongst these compounds, 6h, 6c, and 6h had excellent inhibitory activity against Staphylococcus aureus, and 6h was the best active one. Induced fit docking and MM-GBSA study was showed that compound 6h had binding efficiency and steric interactions in the active site of S. aureus DNA Gyrase (2XCS) with three hydrogen-bonding interactions to residues Arg1122 on chain B, Asp1083 and Arg1122 on chain D, which suggested that the tested compound inhibited this enzyme in S. aureus. [ABSTRACT FROM AUTHOR]

Bioactive molecules displaying visible wavelength emission can be useful for bioimaging, chemosensing and photodynamic therapy applications. Reported herein are 1,3,4-trisubsituted-1,2,3-triazolium salts displaying both antimicrobial and visible emission properties. Using a click chemistry approach, 2-fluorenyl, 1-naphthyl, 2-naphthyl, 2-anthracenyl and 1-pyrenyl units were incorporated at the N1 position, imparting visible emission properties to their triazolium bromide salts with Stokes shifts greater than 100 nm relative to the emission of their triazole precursors. The increasing size of such hydrophobic aryl units impacts minimum inhibitory concentration (MIC) values against Gram-positive bacteria, Gram-negative bacteria and yeast, and can be counterbalanced by hydrophobic substituent variation at other positions of the molecule in order to preserve bioactivity. Among the series of compounds studied are analogs displaying blue, green and yellow colored emission and MIC values as low as 0.4 μM (Gram-positive bacteria), 8 μM (Gram-negative bacteria) and 2 μM (yeast). XRD analysis validates the regioselective benzylation at the N3 position of the 1,2,3-triazole ring and the ability of such compounds to associate through dimeric intermolecular π-stacking interactions. [ABSTRACT FROM AUTHOR]

Reaction of 6-alkoxy-2-oxo-2H-chromen-4-carbaldehydes with N-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)thiosemicarbazide yielded corresponding thiosemicarbazones having 2H-chromen-2-one ring. In vitro evaluations showed that these 2H-chromen-2-one compounds exhibited remarkable antibacterial and antifungal activities against some typical bacteria and fungi. Representative compounds with MIC values of 0.78 − 1.56 μg/mL were 6c, 6g (against S. aureus), 6a, 6f (against S. epidermidis) (Gram-positive bacterial strains), 6e, 6g (against E. coli), 6b, 6e (against K. pneumoniae), and 6d–f (against S. typhimurium) (Gram-negative bacterial strains). Almost all thiosemicarbazones 6a–g had no activity against Gram-positive bacterial strain B. subtilis at these MIC values. Some compounds had strong inhibitory activity against several bacteria, such as 6b (for K. pneumoniae and S. typhimurium), 6d, 6e (for E. coli, K. pneumoniae, and S. typhimurium), 6f (for S. aureus, E. coli, and S. typhimurium), and 6g (for B. subtilis, S. aureus, E. coli, and K. pneumoniae). Some compounds had remarkable inhibitory activity against three clinical MRSA isolates with MIC values of 0.78–6.25 μg/mL. Docking study showed that compound 6g is compatible with the active site of S. aureus DNA gyrase 2XCT, which suggested that the tested compounds inhibited the synthesis of this enzyme. [ABSTRACT FROM AUTHOR]

A need exists to develop safe and efficacious medications to treat major diseases such as cancer and infectious diseases. In response to this need, we synthesized a novel enaminone, which structurally belongs to the trithiocarbonate class engrafted by an enaminone group. The anticancer and antimicrobial activities were evaluated by utilizing three different types of human cancer (MDA-MB-231, LoVo, and HepG2) and a wide field of microbes (G+ and G− bacteria, yeast, and molds). The tested compound 3 exhibited moderate growth suppression activity versus all examined human tumor cells, with values of IC50 ranging from 35 to 45 µg/ml. Moreover, the antimicrobial effects of compound 3 were more profound against fungal pathogens than against bacterial pathogens (minimal inhibitory concentrations; fungi, 0.08–0.14 mg/ml; bacteria, 0.3–1.4 mg/ml). These findings lay the foundation for designing improved bioactive agents that could be utilized as anticancer and/or antimicrobial agents. [ABSTRACT FROM AUTHOR]

Antifungal activity against four yeast of Candida genus of four 1,2,3-triazoles derived from 5-chloro-2(2,4-dichlorophenoxy)phenol, were evaluated in vitro, determining its minimum inhibitory concentration and susceptibility criteria. Strains were exposed to concentrations of 16–0.03 µg/ml, of the four triazoles, following the microplate microdilution technique, using Fluconazole as antifungal control. In all cases 4-[5-Chloro-2-(2,4-dichloro-phenoxy)-phenoxymethyl]-1-(3,4-dichloro-phenyl)-1,2,3-triazole showed the lowest MICs. The four tested triazole derivatives show an effective antifungal effect in vitro in the strains of Candida ATCC, for which it is recommended to carry out microbiological studies in vivo to ensure the efficacy of these compounds in fungal infections developed by Candida spp. [ABSTRACT FROM AUTHOR]

We report a convenient and efficient synthesis of indeno[1,2-c]pyrazol-4(1H)-ones (4a‒o) by the reaction of a variety of 2-acyl-(1H)-indene-1,3(2H)-diones (1) and 2-hydrazinylbenzo[d]thiazole/2-hydrazinyl-6-substitutedbenzo[d]thiazoles (2) in the presence of glacial acetic acid in good yields. The structure of the compounds thus prepared were confirmed by analytical and spectral (FT-IR, 1H NMR, 13C NMR, and HRMS) techniques. All the synthesized indeno[1,2-c]pyrazol-4(1H)-ones (4a‒o) were assayed for their in vitro Type II diabetes inhibitory activity by using Acarbose as standard drug and in vitro antimicrobial activity utilizing Streptomycin and Fluconazole as reference drugs. Among the synthesized derivatives, 4e (IC50 = 6.71 μg/mL) was found to be more potent against α-glucosidase enzyme as compared with the standard Acarbose (IC50 = 9.35 μg/mL) and 4i (IC50 = 11.90 μg/mL) exhibited good inhibitory activity against α-amylase enzyme as compared with the standard Acarbose (IC50 = 22.87 μg/mL). Also, all the titled compounds showed good antimicrobial activity. In addition, in vitro α-glucosidase and α-amylase inhibition were supported by docking studies performed on the derivatives 4e and 4o, respectively. [ABSTRACT FROM AUTHOR]

A novel series of 1,3-bis-(1,2,3-triazol-1-yl)-propan-2-ol derivatives was synthesized from 1-aryl-1,3-diazidopropan-2-ol derivatives and diverse alkynes using copper catalyzed azide-alkyne cycloaddition in the key step. Most of synthesized compounds showed high activity against Candida spp. strains at a 0.04–0.5 μg/mL concentration range compared to Itraconazole and Fluconazole (MIC 2.56 and 1.28 μg/mL, respectively), which were used as reference compounds. A 1,3-bis-(1,2,3-triazol-1-yl)-propan-2-ol derivative (R1 = F and R2 = cyclopropyl) displayed an outstanding selectivity against Candida albicans and Candida krusei (MIC = 0.0075 µg/mL). Moreover, Artemia salina bioassay on 1,3-bis-(1,2,3-triazol-1-yl)-propan-2-ol derivatives revealed low toxicity in this kind of compounds. In addition, molecular docking studies suggest good binding affinity of halogen atoms in some 1-aryl-1,3-diazidopropan-2-ol derivatives to HEME group present in 14-alpha demethylase (CYP51), which might explain the high antifungal activity found in these compounds. [ABSTRACT FROM AUTHOR]

The comparative phytochemical constituents of three Limonium species Limonium myrianthum, Limonium leptophyllum, and Limonium gmelinii afforded a new compound (2 R,3 S)-2,3,4-trihydroxy-2-methylbutyl gallate ( 1) and twenty known compounds ( 2- 21). Each species displayed different profiles in their phytochemical constituents. The isolated compounds ( 1-21) were evaluated for antifungal, antimalarial, and antitrypanosomal activities. Compound 1 showed good activity against chloroquine-resistant and chloroquine-sensitive strains of malaria, while compound 5 displayed moderate antimalarial activity. Compound 14 showed a significant activity against Trypanosoma brucei. [ABSTRACT FROM AUTHOR]

Methyl 3,5-dimethyl pyrazole-1-dithioate (mdpa) ( 1), benzyl 3,5-dimethyl pyrazole-1-dithioate (bdpa) ( 2), 3,5-dimethylpyrazole-1-(5methyl-1 H-pyrazol-3-ylmethyl)-1 H-pyrazole ( 3), copper(II)-mdpa ( 4), copper(II)-bdpa ( 5), cadmium(II)-mdpa ( 6), cadmium(II)-bdpa ( 7), CuS nanoparticles ( 8 and 9) derived from 4 and 5, respectively, CdS nanoparticles ( 10 and 11) derived from 6 and 7, respectively, were synthesized to screen their antimicrobial activities. Prolonged reaction with CuCl.2HO and 3 followed by addition of trace amount of pyridine furnished a crystalline chloro bridged complex [Cu( μ-Cl)(pyridine)] and its structure was solved by single X-ray crystallography. Antibacterial activities of all of the synthesized materials ( 1- 12) were evaluated against Gram positive bacteria including Staphylococcus aureus and Bacillus subtilis and Gram negative bacteria including Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Proteus vulgaris. Fungi ( Candida albicans, Aspergillus flavus) were also used to test antifungal activities with the compounds. Present study revealed that 8 shows best antibacterial activity among the present reported compounds. An excellent antifugal activity is shown by 12 emerging to be a better antibiotic than standard fluconazole. Besides fungicidal effect, 12 has promising larvicidal effect. The structure and activity relationship has been discussed. [ABSTRACT FROM AUTHOR]

( E)-3-(thiophen-2-yl)-1-(4-methylphenyl)-prop-2-en-1-one 1 was obtained from the reaction of thiophene-2-aldehyde with p-methyl acetophenone. The treatment of 1 with guanidine nitrate produced 4-thiophen-2-yl-6-(4-methylphenyl)-pyrimidin-2-ylamine 2. The synthesis of N-substituted benzylidine-4-(4-methylphenyl)-6-(thiophen-2-yl) pyrimidin-2-amines 3a-j was performed by the treatment of compound 2 with the corresponding aromatic aldehydes. The reaction of 3a-j with thioglycolic acid and thiolactic acid formed the corresponding 3-[4-(4-methyl-phenyl)-6-thiophen-2-yl-pyrimidin-2-yl]-2-(substituted-phenyl)-thiazolidin-4-ones 4a-j and 3-[4-(4-methyl-phenyl)-6-thiophen-2-yl-pyrimidin-2-yl]-2-(substituted-phenyl)-5-methyl-thiazolidin-4-ones 5a-j and with chloroacetylchloride, it gives 3-chloro-1-[4-(4-methyl-phenyl)-6-thiophen-2-yl-pyrimidin-2-yl]-4-(substituted-phenyl)-azetidin-2-ones 6a-j. Newer analogues were characterized by infrared spectrum, H nuclear magnetic resonance, C nuclear magnetic resonance spectroscopy and elemental analyses. The newly synthesized analogues were then examined for their antimicrobial activity against some bacterial and fungal strains as two Gram-negative bacteria ( Escherichia coli, Pseudomonas aeruginosa), two Gram-positive bacteria ( Staphylococcus aureus, Streptococcus pyogenes) and two fungal species ( Candida albicans, Aspergillus niger, Aspergillus Clavatus) to develop a novel class of antimicrobial agents. [ABSTRACT FROM AUTHOR]

A series of new pyrazolic heterocyclic compounds were prepared in good and excellent yields and characterized by proton and carbon nuclear magnetic resonance, infrared, and mass spectroscopy studies. These products were screened in vitro against three bacterial pathogens, namely Bacillus subtilis, Micrococcus luteus, and Escherichia coli and antifungal potential, against Fusarium oxysporum f.sp.albedinis. A considerable and excellent activity was recorded with respect to the two studied microorganisms. A good correlation was obtained between the experimental results and the theoretical predictions of bioavailability using Petra/Osiris/Molinspiration suite (Petra/Osiris/Molinspiration containing Lipinski's rule-of-five). The quantitative structure activity relationship approach has been analyzed to support the Petra/Osiris/Molinspiration results and composite indexes of some quantum chemical parameters were constructed in order to characterize the inhibition performance of the tested molecules. [ABSTRACT FROM AUTHOR]

Candidiasis is a serious public health problem that currently affects not only immunodeficient patients with predisposing conditions, but also immunocompetent individuals. Thus, the search for new antifungal agents is required also due to the emergence of resistant strains and to the side effects of the available drugs. The aim of this study is to evaluate the in vitro antifungal profile of nine synthetic 1,2,3-triazole derivatives against four Candida species of medical importance ( C. albicans, C. tropicalis, C. parapsilosis, and C. krusei), as well as to identify their in silico structure-activity relationship. Interestingly, the antifungal susceptibility tests showed the compound 5-methyl-1-(phenylamino)-1H-1,2,3-triazol-4-yl-methanol ( 2b) with the lowest minimal inhibitory concentration value against C. albicans strain (MIC = 8 μg/mL) similar to other promissing compounds described in the literature. According to our in silico evaluation, some stereoelectronic properties (e.g., higher values of log S and lowest unoccupied molecular orbital energy and lower number of atoms, rotatable bonds and Hydrogen bond acceptors) were correlated with the antifungal activity detected. This series reinforced the potential of 1,2,3-triazole as a promising nucleus in the search for new antifungals and may help on designing new drugs for candidiasis. [ABSTRACT FROM AUTHOR]

The azole pharmacophore is still regarded as a viable lead structure for the synthesis of more efficacious and broad-spectrum antimicrobial agents. In this study, a novel series of triazole derivates that are structurally related to the famous antimicrobial azole pharmacophore were synthesized and the structures of them were characterized by spectral (IR, H NMR, C NMR, and MS spectra) analysis. Antimicrobial activity was measured against both bacteria and fungus. In vitro antimicrobial evaluation showed that five compounds had growth inhibitory effects on the tested Gram-positive bacteria and fungus with special efficacy. Potential antibacterial and antifungal activities are incorporated in these triazole compounds. Results of antimicrobial activities also revealed that compounds ( 5a-i) were the potent antibacterial and antifungal agents as compared to standard drugs (ciprofloxacin and itraconazole), and thus could be promising new lead molecules. [ABSTRACT FROM AUTHOR]

Microwave-assisted tandem double condensation between isatins and 4-hydroxycoumarin under zinc triflate catalysis to afford spirooxindoles in excellent yield is reported. The synthesized compounds were screened for their in vitro antibacterial and antifungal activities. The compounds that showed promising antimicrobial activity ( 3a, 3j and 3m) were studied for their binding affinity towards AmpC- β-lactamase receptor, which revealed that compound 3a is highly stabilized by strong hydrogen bond interactions with in the binding pocket. The synthesized spirooxindoles were also evaluated for their cytotoxic potential against COLO320 adenocarcinoma colorectal cancer cells. Biological assay and in silico studies indicated compound 3n as the most active in terms of low IC value (50.7 μM) and least free energy of binding (−8.89 kcal/mol) respectively. [ABSTRACT FROM AUTHOR]

Thirteen, 1,3,5-triazine core containing tetrazole dendrimeric chalcones have been synthesized in three steps. In the first step (1-(4-(1H-tetrazole-1-yl)phenyl)ethanone) is synthesized from sodium azide and triethyl orthoformate. In the second step, the first-generation of dendrimer, 2,4,6-(tris(tetrazole-1-yl-(4-acetylphenyl))-1,3,5-triazine( G1) is generated from cyanuric chloride and 4-tetrazoylacetophenone by Friedel-Crafts reaction. In the third step, 2,4,6-tris(tetrazol-1-yl-(4-phenyl(3-arylpropene-1-on-1-yl))-1,3,5-triazine( G2) dendrimers are prepared from G1 by Claisen-Schmidt reaction with appropriate aldehydes in ethanol at room temperature. The synthesized compounds ( G2, 7a-m) are characterized by Fourier transform infrared (FT-IR), Mass, Matrix-assisted laser ionization Time-of-flight (MALDI-TOF), H nuclear magnetic resonance, C nuclear magnetic resonance, and elemental analysis. Antifungal activities of triazine-based dendrimeric chalcones ( 7a-m) are investigated by minimum inhibition concentration method at different concentrations. Some compounds exhibit moderate activities against tested organisms. Compounds 7b, 7c, and 7f showed good activities and 7l and 7m are emerged as lead molecules showing excellent antifungal activities against a panel of fungi. [ABSTRACT FROM AUTHOR]

Different derivatives of fluoroquinolones were synthesized by combining it with different thiadiazoles. The synthesized compounds were characterized by infrared spectroscopy, proton nuclear magnetic resonance and mass spectral data. The compounds were screened for their antibacterial and antifungal activity. Ciprofloxacin derivatives with thiadiazoles 7c showed good antibacterial as well as antifungal activities, whereas 13c and 13e showed antibacterial and antifungal activity respectively. Sparfloxacin derivative 8c showed both antibacterial and antifungal activity. Sparfloxacin derivatives 14b and 14e showed antibacterial and antifungal activity respectively. [ABSTRACT FROM AUTHOR]

The synthesis of a novel series of substituted 5-(aminomethylene)thiazolidine-2,4-diones was achieved using a wide range of heterocyclic models derived from eight drug-like molecules. The primary aim of this study was to combine medicinally known, biologically active molecules bearing a 2° amine functionality, such as terbinafine, fluoxetine, atomoxetine, cetirizine, risperidone, aripiprazole, ziprasidone, and clopidogrel, with a thiazolidinedione ring via an amino-methylene linker. By targeting this synergistic approach to compounds with skeletal, functional, and stereochemical diversity, we have developed a simple synthetic concept to enrich the thiazolidinedione collection with various biological activities. The biological activities of the newly synthesized 5-(aminomethylene)thiazolidine-2,4-dione derivatives were explored. All compounds were found to have antibacterial activity, with compounds bearing pyridine or piperazine moieties showing good to excellent antibacterial activity. Compounds with piperazine moieties were also found to show good antifungal activity, whereas none of the synthesized compounds showed high cytotoxic activity. [ABSTRACT FROM AUTHOR]

Systematic efforts have been made for the synthesis of moisture stable derivatives of titanium (IV) with both nitrogen- and sulfur-based ligands. New heteroleptic titanium (IV) complexes derived from 8-hydroxyquinoline (HQ) of the types [(Q)Ti{((OiPr)(LOR))(LOR)}] ( 3a- 3c), [(Q)Ti(OiPr)(L)] ( 3d, 3g), [(Q)Ti(LOR)(L)] ( 3e, 3f, 3h, 3i) were prepared by treating the precursor [(Q)Ti(OiPr)] ( 2) with different alkoxyalkanols, 2-hydroxypyridine (HPy), and 2-hetroaryl methyl ketone oxime in different mole ratios using anhydrous toluene as solvent (where, n = 1-2, HQ = 8-HQ, iPr = isopropyl, L = O-CH-CH-, R = CH, CH, R = CH, and LH = 2-HPy, HONC(Me)th-2). Stability study of all these complexes were performed by UV-Visible (UV-Vis) spectroscopy at room temperature and was interpreted on the basis of absorption band arose due to ligand-to-metal charge transfer. All these complexes have good stability against hydrolysis and the shift observed in the absorption band was negligible even after the duration of 72 h persistence in 9:1 mixture of dimethyl sulfoxide and water. All the derivatives were characterized by various physicochemical techniques such as NMR (H, C), Elemental Analysis, Mass, Thermogravimetric Analysis (TGA), FT-IR, and UV-Vis spectroscopy. Monomeric nature of all these derivatives was confirmed by mass spectra. TGA describes the multistage decomposition of complexes at 900 °C. Elemental analyses results are in agreement with the theoretical values. Other spectral data (NMR, FTIR, and UV-Vis) propose the attachment of titanium and ligands in hexa-coordinated fashion. Further, these were subjected for antibacterial and antifungal evaluation against a panel of microorganisms. Complex 3i has shown better activity compared to all its analogs of this series and it was more potent than the standard drugs gentamicin and fluconazole with minimum inhibitory concentrations of 0.017 µM against the Escherichia coli and 0.035 µM for Aspergillus niger, respectively. [ABSTRACT FROM AUTHOR]

A series of novel d-glucose-derived 1,2,3-triazoles have been synthesized in excellent yields via Cu(I)-catalyzed 1,3-dipolar cycloaddition by using methyl α- d-glucopyranoside as starting material. All the new compounds were confirmed by H NMR, C NMR, IR, MS, and HRMS spectra, and their antimicrobial activities were screened against Gram-Positive, Gram-Negative bacteria, and fungi. Bioactive assay manifested that some of the synthesized glucose-derived 1,2,3-triazoles exhibited good antibacterial and antifungal activities. Notably, compound 5k gave the most potent efficiency with MIC value of 6 µM against Candida albicans, which was nine-fold more active than the reference drug Fluconazole. It also exhibited good antibacterial activity against Escherichia coli with the MIC value of 10.8 µM compared to Chloramphenicol while the corresponding hydrochloride 4k revealed remarkable inhibitory against Bacillus subtilis with an MIC value of 11 µM. [ABSTRACT FROM AUTHOR]

A series of novel quinolin-2(1 H)-one derivatives were synthesized and characterized by IR, H NMR, C NMR, and MS spectral data. All the new compounds were screened for their antimicrobial activities against six trains of bacteria and five fungi in vitro by twofold serial dilution technique. The bioactive assay showed that most of the compounds exhibited moderate to good antimicrobial activities in comparison with the streptomycin, especially, compound 6a, the fluoro-substituted aromatic amide derivative, showed good antibacterial activities against B.proteus and P.aeruginosa with minimal inhibitory concentration value of 32 and 16 μg/ml, respectively. [ABSTRACT FROM AUTHOR]

Despite the large number of current antifungals used for treating fungal infections, the increased resistance of these microorganisms over the years has been one of the main and major challenges for medicine in the new century. Thus, it remains necessary to discover novel antifungal agents. The objective of this study was to identify the stereoelectronic features related to the antifungal activity of a series of triazoles and imidazoles derivates with activity against Candida albicans, also pharmacokinetic and toxicity in silico were evaluated to guide the rational design and identification of new antifungal agents. The results showed that features such as maintenance of imidazole ring, the profile of distribution and density of high occupied molecular orbital and conformational aspects in these derivatives were important for the activity and also demonstrate that all the compounds showed good oral bioavailability and low theoretical toxicity profile when compared to antifungals on the market, presenting a promising profile for future in vivo studies. [ABSTRACT FROM AUTHOR]

A new 7-methoxy-2-benzoxazolinone dimer named zeaoxazolinone ( 2), together with four known compounds; 9-Z-hexadecenoic acid ( 1), 6-methoxy-benzoxazolinone ( 3), gallic acid ( 4), and β-sitosterol-3- O- β- d-glucopyranoside ( 5) were isolated from Zea mays L. roots. The structural elucidation of isolated metabolites was established on the basis of UV, IR, 1D, 2D NMR, and MS spectral analyses. Compound 2 exhibited a potent antifungal activity against Aspergillus flavus, Fusarium oxysporum, and Candida albicans. [ABSTRACT FROM AUTHOR]

Candida albicans is one of the most common causes of invasive fungal infections. Azole antifungal agents are widely used as fungal antibiotics which inhibit the cytochrome P450 sterol 14α-demethylase (CYP51). This study describes the homology modeling and three-dimensional model of CYP51 from C. albicans SC5314. Dope score, GA341 of Modeller, PROCHECK statistics, Ramachandran, and G-factors were used to analyze and evaluate a final model. Molecular docking identified the binding mode of the azole antifungal agents with modeled CYP51. The obtained results of Autodock program, compounds 1- 4, were determined the heterocyclic nitrogen atom of azole bound to the heme iron atom in the binding site of the enzyme. Based on the results of this study, we conclude that the structural model of C. albicans SC5314 can be used in azole optimization, virtual screening and de novo inhibitor design for the discovery of new antifungal agents. Graphical Abstract: This study describes the homology modeling and three-dimensional model of CYP51 from C. albicans SC5314. Dope score and GA341 of Modeller, and PROCHECK statistics, Ramachandran, and G-factors were used to analysis and evaluate of the final model. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Some new transition metal complexes with monomethyl succinate are reported. Several physical techniques, such as elemental analysis and melting point, and in addition various spectroscopic techniques including H-, C-NMR and UV/visible and infrared spectroscopy were used to study the chemical structure of the prepared complexes. The octahedral geometry is proposed on the basis of these spectral techniques. The synthesized complexes were also exposed to various bacteria and fungi to establish their bioactivities. [ABSTRACT FROM AUTHOR]

New thiazolidinones 5a- o were prepared from Schiff base 4a- o and thioglycolic acid in the presence of ZnCl from 4-[2-(5-ethylpyridin-2-yl)ethoxy]benzaldehyde. The structures of the synthesized compounds were assigned on the basis of elemental analysis, IR, H NMR C NMR, and mass spectral data. All the compounds were screened against different strains of bacteria and fungi. Compounds 4e, 4n, 4m, 4o, 5e, 5f, 5j, and 5m possessed very good activity against bacterial and fungal species. These active compounds impelled us to study their antitubercular activity. Schiff base 4n and 4e showed M. tuberculosis MIC value 25 and 62.5 μg/ml, respectively. Thiazolidinone 5m displayed M. tuberculosis MIC at 25 μg/ml, which is better antitubercular activity compared with rifampicin. [ABSTRACT FROM AUTHOR]

Benzimidazole analogs bearing electron-withdrawing as well as electron-donating substituent were synthesized to achieve bioactive molecules with significant antimicrobial property. The desired compounds were prepared by multi-step synthesis process. The formation of intermediates and their corresponding derivatives ( III) was confirmed by spectral characterization such as H NMR, C NMR, mass spectra, IR, and elemental analysis. The compounds were screened for their antimicrobial properties against a broad panel of Gram-positive and Gram-negative bacteria as well as fungi. From the SAR study data, it was observed that the derivatives with electron-withdrawing functional groups were more bioactive than that with electron-donating functional groups. [ABSTRACT FROM AUTHOR]

Disubstituted 1,2,4-triazoles 3a- k, 4a- k, and 6a- k have been synthesized from anthranilic acid and nicotinic acid, respectively, through a multi-step reaction sequence via their hydrazides. Synthesized compounds were evaluated for their in vitro antimicrobial activity against two gram-positive bacteria ( S. aureus and B. subtilis), three gram-negative bacteria ( E. coli, S. typhi, and K. pneumonia) as well as four fungi ( A. niger, A. fumigatus, A. flavus, and C. albicans). To explore computational approach, structure-activity relationships were generated statistically using the synthesized compounds and their respective quantitative values of biological activities. These models can be used in future for predicting antimicrobial activity on similar class of compounds. [ABSTRACT FROM AUTHOR]

The study was aimed at the syntheses and evaluation of a series of novel 3-benzyl-2,6-diarylpiperidine-4-ones. The newly synthesized compounds were characterized by elemental analysis, infrared, H NMR, C NMR, and mass spectral analyses. These compounds were screened for their inhibiting potential against various bacterial and fungal strains. The antimicrobial activity was performed against four Gram positive bacteria ( S. aureus, B. subtilis, B. pumilus, and M. luteus), three Gram negative bacteria ( P. aeruginosa, P. fluorescens, and E. coli), and two fungal strains ( A. niger and P. chrysogenum) by cup-plate method and tube assay method. The results reveal that some of these compounds exhibited remarkable activity against the selected bacterial and fungal strains, with MIC values as low as 50 μg/mL. Interestingly, all the compounds exhibited better antifungal activity than antibacterial activity. Thus, it can be concluded that 3-benzyl-2,6-diarylpiperidine-4-ones may exhibit potent antifungal activity. [ABSTRACT FROM AUTHOR]

A new series of 2-((4-(2 H-benzo[ d][1,2,3]triazol-2-yl)piperidin-1-yl)methyl)-5-substituted-1-yl)-acetic acid hydrazide ( 3) with various substituted aromatic carboxylic acids phenyl-1,3,4-oxadiazoles ( 4a- j) were synthesized by cyclization of 4-benzotriazol-2-yl-piperidin in the presence of POCl. The structures were characterized by spectral data. The representative examples were screened invitro antibacterial activity and antifungal activity. The compounds showed significant antibacterial activity and showed moderate antifungal activity as that of standards, respectively. The data were further compared with structure-based investigations using docking studies with the crystal structure of oxidoreductase (1XDQ) protein organism: Escherichia coli for antibacterial activity and oxidoreductase (3QLS) protein, organism: Candida albicans for antifungal activity. The score values estimated by genetic algorithm were found to have a good correlation with the experimental inhibitory potencies. [ABSTRACT FROM AUTHOR]

A series of mono and bis N-Mannich bases incorporating 3-(4-methylphenyl)-4-(substituted-1/4-ylmethyl)sydnone scaffolds were synthesized and tested for their antibacterial, antifungal, anticancer, and antiviral activities. Most of the compounds showed moderate-to-significant antibacterial and antifungal activities. The compounds did not show selective activity against HIV. Some of the compounds have been evaluated for anticancer activity, but they were found as poorly active. The structures of the synthesized compounds were elucidated by IR and NMR spectroscopy. [ABSTRACT FROM AUTHOR]

A series of N-aryl-substituted 5-fluoroisatin-3-thiosemicarbazones 3a-3l was synthesized and evaluated for selected biological activities. The brine shrimp lethality bioassay was carried out to study their in vitro cytotoxicity potential and besides, their antifungal, phytotoxic and urease inhibitory effects were also investigated. Seven compounds i.e. 3a, 3d, 3f, 3g, 3h, 3j and 3k proved to be active in the brine shrimp assay, displaying promising cytotoxicity (LD = 6.89 × 10-2.79 × 10M). Amongst these, 3a and 3h were found to be the most active ones (LD = 6.89 × 10 and 9.79 × 10M, respectively). Compounds 3i, 3j and 3 k displayed moderate (40 %) antifungal activity against one or two fungal strains i.e. A. flavus and/or M. canis. In phytotoxicity assay, all the synthesized compounds, including the reference point 2m showed weak-to-moderate (15-70 %) activity at the highest tested concentration (500 μg/mL). In urease inhibition assay, compounds 3f, 3g and 3j proved to be the most potent inhibitors, demonstrating relatively a higher degree of enzymatic inhibition with IC values ranging from 37.7 to 47.3 μM. [ABSTRACT FROM AUTHOR]

Synthesis and biological evaluation of substituted pyrimidine derivatives containing 4-amino and 5-cyano substituted derivatives are described. Biginelli typed three component reactions between an aldehyde, malononitrile, and a urea constituent give a rapid facile pyrimidine ring. The constitution of the products has been delineated by elemental analysis and spectral analysis. The products were assayed for their in vitro biological assay antibacterial activity against S. pyogenes MTCC- 442, S. aureus MTCC- 96, E. coli MTCC- 443, and B. subtilis MTCC- 441 bacterial strain and antifungal activity against Aspergillus niger MTCC- 282 and Candida albicans MTCC- 227 at different concentrations, which compared with Ampicillin, Chloramphenicol, Ciprofloxacin, Norfloxacin, and Griseofulvin as standard drug which are presented. [ABSTRACT FROM AUTHOR]

In search of pharmalogically active molecules in the class of oxadiazoles, the present article deals with the synthesis of 5-(5′-fluoro-2′-methoxybiphenyl-3-yl)-1,3,4-oxadiazol-2(3 H)-one 2 from its hydrazide analog 1. The compound 2 was regioselectively N-alkylated with alkyl halides and produced the compounds 3a- f. Compound 3f was further functionalized with substituted benzenesulfonyl chlorides to give compounds 3g- j. The synthesized compounds were characterized by elemental and spectral analysis. Newly synthesized compounds were tested for their in vivo anti-inflammatory, analgesic, and in vitro antimicrobial activities. The compounds 3a- c were found to have promising anti-inflammatory and analgesic activities. Compounds 3b, 3f, and 3g showed significant antibacterial and antifungal activities. [ABSTRACT FROM AUTHOR]

A data set of 31 benzimidazole derivatives with antibacterial activities against gram-positive (e.g. Staphylococcus aureus, methicillin-resistant S. aureus (MRSA) and Bacillus subtilis) and gram-negative (e.g. Escherichai coli) bacteria as well as antifungal (e.g. Candida albicans) activity were used for quantitative structure-activity relationship (QSAR) study. Compounds were characterized by quantum chemical descriptors calculated at B3LYP/6-31G(d) level and molecular descriptors generated using Dragon software. The QSAR model was constructed using multiple linear regression method and sampled by leave-one-out cross-validation and the predictive performance can be deduced from the correlation coefficient ( r), which was in the range of 0.4194-0.8485 while root mean square error (RMSE) was in the range of 0.039-0.3247. Particularly, QSAR model against S. aureus, MRSA (clinical isolates) and E. coli provided good predictive ability with r values of 0.8485, 0.8443 and 0.833, respectively, and RMSE values of 0.2662, 0.2488 and 0.039, respectively. The QSAR models demonstrated high potential for the rational design of novel benzimidazole derivatives with potent antimicrobial activities. [ABSTRACT FROM AUTHOR]

A series of novel sulfonyl derivatives 3-(substituted benzylsulfonyl)-5-(4-isopropylthiazol-2-yl)-4-phenyl-4H-1,2,4-triazoles 4a- 4e, isopropyl thiazole-derived schiff bases 8a- 8l, and 2-(substituted benzylsulfonyl)-5-(4-isopropylthiazol-2-yl)-1,3,4-oxadiazoles 11a- 11e were synthesized and characterized by IR, H NMR, C NMR, elemental, and mass spectral analysis. All the compounds exhibited moderate to significant antibacterial and antifungal activities. Results of the antitubercular screening against Mycobacterium tuberculosis H37Rv ascertain compounds 4e, 8b, and 8f as excellent antitubercular molecules, when compared with first line drug isoniazid (0.25 μg/mL). [ABSTRACT FROM AUTHOR]

A newly synthesised series of antibacterial and antifungal triazole-derived Schiff base ligands ( L) -( L) has been prepared by the condensation reaction of 3,5-diamino-1,2,4-triazole with methyl-, chloro- and nitro-substituted thiophene-2-carboxaldehydes in (1:2) molar ratio. The most probable structures of the synthesised Schiff base ligands were established on the basis of their physical, spectral (IR, H and C NMR and mass spectrometry) and analytical (CHN analysis) data. These Schiff bases potentially act as bidentate ligand and were further made to react with the vanadyl(IV) sulphate (VOSO·5HO) in (1:2) (metal:ligand) molar ratio to prepare their oxovanadium(IV) complexes ( 1) -( 5). All oxovanadium(IV) complexes showed a square-pyramidal geometry which was established on the basis of their physical, spectral and analytical data. The Schiff base ligands and their vanadyl(IV) complexes have been screened for their in vitro antibacterial, antifungal and brine shrimp bioassay. The antimicrobial activity data showed the vanadyl(IV) complexes to be more potent antibacterial and antifungal than the parent Schiff bases against one or more bacterial and fungal species. [ABSTRACT FROM AUTHOR]

Ten newly synthesized thiosemicarbazones of piperazine ( 3a- 3j) were evaluated for their antibacterial and antifungal activity against non-pathogenic strains of Escherichia coli (NCIM 2068), Klebsiella pneumonia (NCIM 2957), Staphylococcus aureus (NCIM 2079), and Bacillus subtilis (NCIM 2921); pathogenic strains of Vibrio cholerae, protease, Candida albicans and Aspergillus niger. All the 10 compounds ( 3a- 3j) were found to be better than Ciprofloxacin against B. subtilis and four molecules ( 3c, 3d, 3e, and 3h) against S. aureus. Compound 3j, a derivative of benzophenone, has been identified as a potent and promising candidate against C. albicans. The compounds were also evaluated for their anticancer activity against HBL-100 and HL60 cell lines. Compound 3a, a p-hydroxy benzaldehyde derivative, has been identified as a potent and promising candidate. [ABSTRACT FROM AUTHOR]

In this study, various substituted chalcones, prepared by condensing substituted acetophenones with substituted aldehydes/arylfurfurals, were treated with thiosemicarbazide in basic media to produce 1-thiocarbonyl-3,5-disubstituted pyrazolines which on further reaction with substituted phenacyl bromides afforded the title compounds in good yield. Structures of the newly synthesized compounds were assigned on the basis of elemental analyses, IR, H NMR, and mass spectral studies. The newly synthesized compounds were tested for their in vitro antibacterial and antifungal activities against a variety of microorganisms and antioxidant activities by diphenylpicrylhydrazyl radical scavenging assay. Among the derivatives, compounds 3b, 3e, 6a, and 6h were identified as potent antioxidants. Compounds 3 d, 3e, and 6a- f have emerged as the most promising antimicrobial agents displaying the maximum activity against all the tested microorganisms. [ABSTRACT FROM AUTHOR]

Several bischalcones ( 2a- h and 5a- e) and flavones ( 3a- f) were synthesized and evaluated for their antimicrobial actions. Bischalcones were prepared by condensing 1,1′-(4,6-dimethyl-1,3-phenylene)diethanone ( 1) or 1-(5-acetyl-2,4-dimethoxyphenyl)-1-ethanone ( 4) with arylaldehydes. Bischalcones were cyclized in presence of iodine to give corresponding flavones ( 3a- f). An alternative route to synthesize the flavones consisted in preparing the diester derivatives ( 6a- f) of ( 1) with different aromatic acids, which could be converted to β-diketones followed by cyclization to give the corresponding flavones. However, all the attempts in this direction were unsuccessful and it could not be possible to proceed beyond diester stage; six diester derivatives ( 6a- f) were synthesized. The structures of the synthesized compounds were assigned on the basis of H NMR, mass spectral data and microanalyses results. The antimicrobial screening was performed at a concentration of 100 μg/mL by cup plate method; the compounds inhibiting growth of one or more of the microorganisms were further tested for their minimum inhibitory concentration (MIC) by turbidity method. Preliminary antimicrobial results revealed that the compounds 2a- h and 3a- f were significant in their antibacterial and antifungal activities. MICs results showed that the compound 2f exhibited very good activity against E. coli, P. aeruginosa, and C. albicans with MIC-12.5 μg/mL. Similar type of activity was shown the compound 3a against S. aureus and C. albicans with MIC-12.5 μg/mL. Another compound, 3f, was active against P. aeruginosa and C. albicans with MIC-12.5 μg/mL. Methylation of the two chelated hydroxyls ( 5a- e) significantly reduced the activity. However, oxidative cyclization of bischalcones resulted in compounds ( 3a- f) which were found to be considerably active. Diesters ( 6a- f) were insignificant in their antimicrobial activities. [ABSTRACT FROM AUTHOR]

A series of novel positional isomers of 1-alkyl-2-trifluoromethyl benzimidazole derivatives 3a- j and 4a- j have been synthesized and screened for antibacterial activity against gram positive bacteria viz, Bacillus subtilis, Staphylococcus aureus and gram negative bacteria viz., Escherichia coli, Pseudomonas aeruginosa and antifungal activity against Candida albicans, Aspergillus niger, Rhizopus oryzae and Saccharomyces cerevisiae. Results indicate that compounds 3b, 4b were having promising antibacterial and antifungal activity. [ABSTRACT FROM AUTHOR]