Azole-Based Antibacterial Agents: A Review on Multistep Synthesis Strategies and Biology (original) (raw)
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Synthesis and evaluation of antimicrobial properties of some azole derivatives
Tropical Journal of Pharmaceutical Research
Purpose: To synthesize new azole derivatives and determine their antimicrobial properties. Methods: The reaction of the intermediates (2a-2c) with 3a-3c in acetone/potassium carbonate solution yielded 4a-4i, which were characterized using Fourier-transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (1H-NMR), carbon-13 nuclear magnetic resonance (13C-NMR)) and mass spectrometry (MS). Compounds 4a-4i were assessed for their antibacterial and antifungal effects using the sequential dilution technique, relative to ofloxacin and ketoconazole. Results: The spectral data for 4a-4i were consistent with the assigned structures. The MIC of compound 4h (10 μg/ml) was similar to that of ketoconazole against Aspergillus flavus, Penicillium citrinum, and Aspergillus niger. The MIC value of compound 4b (10 μg/ml) for Penicillium citrinum was comparable to that of ketoconazole while the MIC value of compound 4d against Staphylococcus aureus and Escherichia coli (20 μg/ml) was e...
A fascinating decade for the synthesis of 1,2-azoles
Heterocyclic Communications, 2013
1,2-Azoles comprising pyrazoles, isoxazoles, and isothiazoles have occupied a distinctive position in the design and synthesis of novel biologically active compounds that exert remarkable pharmaceutical activities as medicines and agrochemicals. As a consequence, there has been an increasing interest among synthetic organic/ medicinal chemists in the development of methodologies for the rapid access to these heterocycles. In this review, we have summarized the most significant advances in the construction of functionalized pyrazoles, isoxazoles, and isothiazoles reported in the literature up to 2012.
Cytotoxic evaluation of some new and potent azole derivatives as antimicrobial agents
2017
Recently use of antifungal drugs in human medicine has been increased, especially with the advent of AIDS epidemic. Despite the growing list of azoles, their clinical value has been limited by their relatively high risk of toxicity and the emergence of drug resistance. Efforts have focused on the development of new, less toxic and more efficacious antifungal agents. We previously described synthesis of some new azole derivatives. We also evaluated all the synthesized compounds for their antifungal activity. Most of our compounds showed desirable activity against different species of microorganisms. Here we choose thirteen of these compounds, 5 bentriazole derivatives (1a-5a) , 5 imidazole derivatives (1b-5b) and 3 triazole derivatives (1c-3c) to evaluate their cytotoxic activities against a human cancer cell line (MCF-7) using colorimetric MTT cytotoxic assay. Their cytotoxic activities were compared to clotrimazole as a positive control. Our results collectively showed that most o...
Bioorganic & Medicinal Chemistry Letters, 2010
In an attempt to find novel azole antifungal agents with improved activity and broader spectrum, computer modeling was used to design a series of new azoles with piperidin-4-one O-substituted oxime side chains. Molecular docking studies revealed that they formed hydrophobic and hydrogen-bonding interactions with lanosterol 14a-demethylase of Candida albicans (CACYP51). In vitro antifungal assay indicates that most of the synthesized compounds showed good activity against tested fungal pathogens. In comparison with fluconazole, itraconazole and voriconazole, several compounds (such as 10c, 10e, and 10i) show more potent antifungal activity and broader spectrum, suggesting that they are promising leads for the development of novel antifungal agents.
Antibacterial Activity of Some New Azole Compounds
Anti-Infective Agents, 2012
The development of antimicrobial agents to treat infections has been one of the most notable medical achievements of the past century. Despite the growing list of azoles, their clinical value has been limited by their relatively high risk of toxicity and the emergence of drug resistance. This necessitates the development of more effective broad spectrum antimicrobials with fewer side effects. We previously described the design and synthesis of some new azole derivatives in both imidazole and triazole groups. Here we selected 30 analogues of them in 4 different categories (imidazoles (1), benzimidazoles (2), triazoles (3) and benztriazoles (4)) and investigated their antibacterial activity against different species of gram positive and gram negative microorganisms. Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Bacillus subtilis as gram positive and Escherichia coli, Salmonella typhi, Shigella sonnei, Pseudomonas aeroginosa and Proteus vulgaris as gram negative bacteria were chosen. Disc plate method and serial dilution assay were used to establish the minimum inhibitory concentration of the above compounds. The results show compounds 1-dodecyl-2-methyl-1H-imidazole (1g), 2-(1H-1-imidazolyl)-1-cyclohexanol (1a) and 2-(2-methyl-4-nitro-1H-1-imidazolyl)-1cyclohexanol (1o) had desirable antibacterial activity on both gram positive and gram negative species. Compounds 1trityl-1H-benzo (d) imidazole (2a) and 1-octyl-1H-1,2,4-triazole (3b) had higher effect for gram positive and gram negative bacteria respectively. Compounds 2-methyl-1-nonyl-1H-imidazole (1f) and 1-butyl-2-methyl-4-nitro-1H-imidazole (1l) had moderate activity for gram negative bacteria.
Bioorganic & medicinal …, 2009
A series of novel enantiomerically pure azole derivatives was synthesized. The new compounds, bearing both an imidazole as well as a triazole moiety, were evaluated as antimycobacterial agents. One of them proved to have activity against Mycobaterium tuberculosis comparable to those of the classical antibacterial/antifungal drugs Econazole and Clotrimazole. Tuberculosis (TB) is a common and deadly infectious disease caused by mycobacteria, mainly Mycobacterium tuberculosis. Over one-third of the world's population has been exposed to the TB bacterium, and new infections occur at a rate of one per second. 1 In 2005, mortality and morbidity statistics included 14.6 million chronic active TB cases, 8.9 million new cases, and 1.6 million deaths, mostly in developing countries. 2 In addition, the rising number of people who are contracting TB because of their immune systems compromised by immunosuppressive drugs or substance abuse or HIV/AIDS, is a serious threat to TB control and prevention. Moreover the emergence of multi-drug resistance TB (MDR-TB), defined as resistance to at least isoniazid and rifampin, and the extensively drug resistant (XDR-TB) strains make the discovery and the development of new drugs a priority. 3 In the last few years, the determination of the genome sequence of Mycobacterium tuberculosis 4,5 (MTB) provided a much needed boost for research into new drug targets against this pathogen. In particular, recent promising data suggest that targeting the lipid metabolism pathways of MTB may provide an excellent route to attenuating or killing the bacterium. The genome of MTB encodes for a relatively large number of cytochrome P450 enzymes. These data indicate important physiological roles for these enzymes which, given that the substrate preference of the majority of P450s is for hydrophobic molecules, most are likely to be involved in lipid metabolism. McLean and co-workers cloned and expressed MTB CYP51 and CYP121, two types of P450 from MTB. 6 They demonstrated that CYP51 and CYP121 bind azole antifungal drugs tightly and that azole compounds are potent inhibitor of cell growth of Mycobacterium bovis and Mycobacterium smegmatis, two mycobacterial species which closely resemble MTB. Azole drugs proved to have also antitubercular activities in mice. 7 Finally, recent studies furnished the crystal structure of MTB cytochrome P450 CYP121 in complex with the fluconazole. 8 It has been found that MTB-CYP121 binds commercially available azole drugs as clotrimazole or econazole and that it may be the true target for the antimycobacterial activity of the azoles in vivo as suggested by gene-knockout studies. In this context, as a continuation of our previous works on the discovery of new antimicrobial agents, 11,12 we decided to focus our attention on the synthesis and preliminary biological evaluation against MTB of novel azole analogues with polycyclic structure A which resemble the classical antifungal/antibacterial azole drugs . Being the target compounds chiral, we were also attracted by the possibility of synthesizing these derivatives in enantiomerically pure form in order to evaluate the biological profile of the single enantiomers.
Green synthesis and biological evaluation of some novel azoles as antimicrobial agents
Bioorganic & Medicinal Chemistry Letters, 2010
In this study, we describe a green and simple procedure for the synthesis of steroidal 2Hpyrans 4-6 using chitosan as an eco-friendly heterogeneous catalyst. The synthesized compounds were characterized by IR, 1 H NMR, 13 C NMR, MS and analytical data. These compounds were tested in vitro against two cancer cell lines [HeLa (cervical) and Jurkat (leukemia)] and one normal cell line (PBMC). The compounds exhibited moderate to good activity against the two human cancer cell lines and were less toxic against the non-cancer cell line. In addition, the synthesized compounds were tested for their in vitro antioxidant activity by 1,1-diphenylpicrylhydrazyl method in which compounds 4 and 6 exhibited good antioxidant activity. This study provided a new molecular scaffold for the further development of anticancer as well as antioxidant agents.
Design, synthesis and evaluation in vitro antibacterial activity of new 1,2,3-triazole derivatives
PROCEEDING OF THE 1ST INTERNATIONAL CONFERENCE ON ADVANCED RESEARCH IN PURE AND APPLIED SCIENCE (ICARPAS2021): Third Annual Conference of Al-Muthanna University/College of Science
In the current work, 1,2,3-triazole and 1,3,4-thiadiazole rings were combined in the same structure via a multisteps synthetic pathway to present a series of 1,2,3-triazole derivatives. The newly synthesized compounds were characterized by FT-IR, 1H-NMR, 13C-NMR and mass spectra. The final compounds and their precursors were in vitro tested as antibacterial agents by well diffusion method against the Gram-negative strains (Helicobacter Pylori, Klebsiella pneumonia, Escherichia coli O157) and the Gram-positive strain of Staphylococcus aureus. The bioassay indicated that all the tested compounds were not active or possessed a week to excellent antibacterial activity depending on the type of the tested bacteria and the structure of the target compounds.