scholarly journals Synthesis, antimicrobial activities and GAPDH docking of novel 1, 2, 3-triazole derivatives

2021 ◽  
Vol 18 (5) ◽  
pp. 1101-1108
Author(s):  
Abdulsalam A.M. Alkhaldi ◽  
Mohamed A. Abdelgawad ◽  
Bahaa G.M. Youssif ◽  
Ahmed O. El-Gendy ◽  
Harry P. De Koning
Keyword(s):  
Staphylococcus Epidermidis ◽  
Antimicrobial Agents ◽  
Leishmania Major ◽  
Antimicrobial Activities ◽  
Docking Studies ◽  
Moderate Activity ◽  
Triazole Derivatives ◽  
Lead Compounds ◽  
Compound Ii

Purpose: To synthesize new triazole derivatives in order to overcome the problem of side effects of antimicrobial agents and microbial resistance, while broadening the spectrum of antimicrobial activity. Methods: The starting triazole, compound 1, was prepared through click chemistry and reacted with chloroacetyl chloride to yield compound II. Triazole 1 was reacted with acids and aldehydes to produce oxadiazole (III) and azomethine (IV) which cyclized in acetic anhydride to give a new acetylated oxadiazole (V). Minimum inhibitory concentration (MIC) and resorufin assays were used for antibacterial and anti-parasitic screening, respectively. Compounds II and IVb were subjected to molecular docking studies using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) Molecular Operating Environment (MOE) program. Results: Novel oxazole-triazole derivative (III) showed high activity against Pseudomonas aeruginosa and moderate activity against Staphylococcus epidermidis, whereas compound IVc showed moderate activity against Staphylococcus epidermidis. Chloro-acetyl-triazole II and 2-hydroxyphenyl-triazole Schiff base (Ivb) showed pronounced activity against the kinetoplastid parasites, Leishmania major, Leishmania mexicana and Trypanosoma brucei. Conclusion: The new synthesized triazoles represent a new antimicrobial scaffold and identifies potential new lead compounds for follow-up and for further mechanistic studies.

Design and synthesis of new antifungals based on N- un-substituted azoles as 14α demethylase inhibitor

2020 ◽  
Vol 16 ◽  
Author(s):  
Asghar Davood ◽  
Aneseh Rahimi ◽  
Maryam Iman ◽  
Parisa Azerang ◽  
Soroush Sardari ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Antifungal Agents ◽  
Molecular Design ◽  
Pathogenic Fungi ◽  
Antimicrobial Activities ◽  
Docking Studies ◽  
Receptor Interaction ◽  
Main Role ◽  
Design And Synthesis ◽  
Antifungal Antibiotics

Objective(s): Azole antifungal agents, which are widely used as antifungal antibiotics, inhibit cytochrome P450 sterol 14α-demethylase (CYP51). Nearly all azole antifungal agents are N-substituted azoles. In addition, an azolylphenalkyl pharmacophore is uniquely shared by all azole antifungals. Due to importance of nitrogen atom of azoles (N-3 of imidazole and N-4 of triazole) in coordination with heme in the binding site of the enzyme, here a group of N- un-substituted azoles in which both of nitrogen is un-substituted was reported. Materials and Methods: Designed compounds were synthesized by reaction of imidazole-4-carboxaldehyde with appropriate arylamines and subsequently reduced to desired amine derivatives. Antifungal activity against Candida albicans and Saccharomyces cervisiae were done using a broth micro-dilution assay. Docking studies were done using AutoDock. Results: Antimicrobial evaluation revealed that some of these compounds exhibited moderate antimicrobial activities against tested pathogenic fungi, wherein compound 3, 7 and 8 were potent. Docking studies propose that all of the prepared azoles interacted with 14α-DM, wherein azole-heme coordination play main role in drug-receptor interaction. Conclusion: Our results offer some useful references in order to molecular design performance or modification of this series of compounds as a lead compound to discover new and potent antimicrobial agents.

scholarly journals SYNTHESIS CHARACTERIZATION AND ANTIMICROBIAL ACTIVITIES STUDIES OF N-{2-(4-CHLOROPHENYL) ACETYL} AMINO ALCOHOLS DERIVED FROM α-AMINO ACIDS

2020 ◽  
pp. 11-16
Author(s):  
G. Venkateshappa ◽  
G. Shivaraju ◽  
P. Raghavendra Kumar
Keyword(s):  
Amino Acids ◽  
Amino Alcohols ◽  
Antimicrobial Activities ◽  
Docking Studies ◽  
Moderate Activity ◽  
E Coli ◽  
Synthetic Drugs ◽  
Antimicrobial Studies ◽  
Ft Ir ◽  
Derivatives Of

Amino acids play important roles in organisms to sustain in living state and perform as body constituents, enzymes and antibodies. At insalubrious situations, use of amino acids derivatives as drugs in the maintenance of normal health is better choice than common unnatural synthetic drugs. This is due to the fact that the amino acids derivatives may be more bio-compatible, biodegradable and eliminate easily than others.  In this sense we have made an effort and report herein the synthesis of N-{2-(4-chlorophenyl) acetyl} amino alcohols synthesised by reduction of N-{2-(4-chlorophenyl)acetyl} derivatives of (S)-amino acids such as (S)-phenylalanine, (S)-alanine, (S)-methionine, (S)-leucine, (S)-tryptophan and (S)-proline. These newly synthesized amino acids derivatives were analysed by proton, carbon-13 NMR and FT-IR spectroscopy. The composition of solid derivatives was determined by elemental analysis. Further, antimicrobial activities of these derivatives were assessed on usual bacteria K. aerogenes, E. coli, S. aureus and P. desmolyticum and fungi A. flavus and C. albicans. The compounds were witnessed moderate activity than authorised antibacterial and fungal agents Ciprofloxacin and Fluconazole respectively. The antimicrobial studies also revealed that, these derivatives could be better antifungal agents than antibacterial agents. Finally we compared the experimental results of antimicrobial activities with docking studies.  

scholarly journals Synthesis of Novel 1,2,4-Triazole Derivatives as Antimicrobial Agents via the Japp-Klingemann Reaction: Investigation of Antimicrobial Activities

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Tasneem Taj ◽  
Ravindra R. Kamble ◽  
Atukuri Dorababu ◽  
Gangadhar Y. Meti
Keyword(s):  
Antimicrobial Activity ◽  
Oral Bioavailability ◽  
Antimicrobial Agents ◽  
Antimicrobial Activities ◽  
Triazole Derivatives ◽  
Drug Score

In the present investigation, 1,2,4-triazole appended to pyrazoline and pyrazole rings (4a–g) using N-arylsydnone as synthon was prepared. The title compounds were subjected to Osiris property explorer for the oral bioavailability to analyze their drug likeness and drug score. Further, the compounds were subjected to the antimicrobial activity and analyzed the IC 50 and MIC values.

scholarly journals Development of New Antimicrobial Oleanonic Acid Polyamine Conjugates

Antibiotics ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 94
Author(s):  
Elmira F. Khusnutdinova ◽  
Véronique Sinou ◽  
Denis A. Babkov ◽  
Oxana Kazakova ◽  
Jean Michel Brunel
Keyword(s):  
Antimicrobial Agents ◽  
Antimicrobial Activities ◽  
Successful Outcome ◽  
Moderate Activity ◽  
E Coli ◽  
Starting Point ◽  
Oleanonic Acid ◽  
Acid Conjugate ◽  
Polyamine Conjugates ◽  
Almost All

A series of oleanolic acid derivatives holding oxo- or 3-N-polyamino-3-deoxy-substituents at C3 as well as carboxamide function at C17 with different long chain polyamines have been synthesized and evaluated for antimicrobial activities. Almost all series presented good to moderate activity against Gram-positive S. aureus, S. faecalis and B. cereus bacteria with minimum inhibitory concentration (MIC) values from 3.125 to 200 µg/mL. Moreover, compounds possess important antimicrobial activities against Gram-negative E. coli, P. aeruginosa, S. enterica, and EA289 bacteria with MICs ranging from 6.25 to 200 µg/mL. The testing of ability to restore antibiotic activity of doxycycline and erythromycin at a 2 µg/mL concentration in a synergistic assay showed that oleanonic acid conjugate with spermine spacered through propargylamide led to a moderate improvement in terms of antimicrobial activities of the different selected combinations against both P. aeruginosa and E. coli. The study of mechanism of action of the lead conjugate 2i presenting a N-methyl norspermidine moiety showed the effect of disruption of the outer bacterial membrane of P. aeruginosa PA01 cells. Computational ADMET profiling renders this compound as a suitable starting point for pharmacokinetic optimization. These results give confidence to the successful outcome of bioconjugation of polyamines and oleanane-type triterpenoids in the development of antimicrobial agents.

scholarly journals Screening and Molecular Docking of Novel Benzothiazole Derivatives as Potential Antimicrobial Agents

Antibiotics ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 221 ◽  
Author(s):  
Mohamed A. Morsy ◽  
Enas M. Ali ◽  
Mahmoud Kandeel ◽  
Katharigatta N. Venugopala ◽  
Anroop B. Nair ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Candida Albicans ◽  
Aspergillus Niger ◽  
Active Site ◽  
Antimicrobial Agents ◽  
Hydrophobic Interactions ◽  
Antimicrobial Activities ◽  
Moderate Activity ◽  
Benzothiazole Derivatives

The burden of antibiotic resistance necessitates a continued search for new antimicrobials. We evaluated the antimicrobial activities of novel benzothiazoles synthesized by our group. Antibacterial activity was evaluated in vitro in Staphylococcus aureus, Bacillus subtilis, and Escherichia coli, while the antifungal activity was tested in Candida albicans and Aspergillus niger, and expressed as the minimum inhibitory concentration (MIC; µg/mL). MIC values of benzothiazole compounds ranged from 25 to 200 µg/mL. Compounds 3 and 4 gave high antibacterial and moderate antifungal activities, while 10 and 12 showed moderate activity against all tested organisms. In addition, some benzothiazole compounds significantly suppressed the activity of Escherichia coli dihydroorotase and inhibited the dimorphic transition of Candida albicans. Moreover, the active benzothiazole compounds induced DNA and protein leakage in Aspergillus niger spores. Molecular interactions of benzothiazole derivatives with dihydroorotase revealed the formation of hydrogen bonds with the active site residues LEU222 or ASN44. Strong hydrophobic interactions of the bulky thiazole and naphthalene rings at the entrance to the active site might interfere with the access of substrates to their binding sites, which results in dihydroorotase inhibition. Thus, inhibition of dihydroorotase might contribute to the observed antimicrobial actions of these compounds.

scholarly journals Design, synthesis and docking studies of novel thiazole derivatives incorporating pyridine moiety and assessment as antimicrobial agents

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rizk E. Khidre ◽  
Ibrahim Ali M. Radini
Keyword(s):  
Antimicrobial Agents ◽  
Docking Simulation ◽  
Antibacterial Activities ◽  
Antimicrobial Activities ◽  
Docking Studies ◽  
The Novel ◽  
Thiazole Derivatives ◽  
Design Synthesis ◽  
Pyridine Moiety ◽  
In Silico Molecular Docking

AbstractA novel series of substituted 4,6-dimethyl-2-oxo-1-(thiazol-2-ylamino)-1,2-dihydropyridine-3-carbonitrile derivatives 6, 9, 13, 15, and 17 was synthesized in a good to excellent yield from the reaction of 1-(3-cyano-4,6-dimethyl-2-oxopyridin-1(2H)-yl)thiourea with 2-oxo-N'-arylpropanehydrazonoyl chloride, chloroacetone, α-bromoketones, ethyl chloroacetate, and 2,3-dichloroquinoxaline, respectively. The potential DNA gyrase inhibitory activity was examined using in silico molecular docking simulation. The novel thiazoles exhibit dock score values between − 6.4 and − 9.2 kcal/mol and they were screened for their antimicrobial activities. Compound 13a shown good antibacterial activities with MIC ranged from 93.7–46.9 μg/mL, in addition, it shown good antifungal activities with MIC ranged from 7.8 and 5.8 μg/mL.

New vinyl-1,2,4-triazole derivatives as antimicrobial agents: Synthesis, biological evaluation and molecular docking studies

2020 ◽  
Vol 30 (17) ◽  
pp. 127368
Author(s):  
Eugenia Stingaci ◽  
Marina Zveaghinteva ◽  
Serghei Pogrebnoi ◽  
Lucian Lupascu ◽  
Vladimir Valica ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antimicrobial Agents ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Triazole Derivatives ◽  
Molecular Docking Studies

Synthesis and Biological Evaluation of the Antimicrobial Natural Product Lipoxazolidinone A

2018 ◽  
Author(s):  
Jonathan J. Mills ◽  
Kaylib R. Robinson ◽  
Troy E. Zehnder ◽  
Joshua G. Pierce
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Mechanism Of Action ◽  
Marine Natural Products ◽  
Biological Evaluation ◽  
Lead Compounds ◽  
Follow Up Studies ◽  
Initial Resistance ◽  
Synthesis And Biological Evaluation

The lipoxazolidinone family of marine natural products, with an unusual 4-oxazolidinone heterocycle at their core, represents a new scaffold for antimicrobial discovery; however, questions regarding their mechanism of action and high lipophilicity have likely slowed follow-up studies. Herein, we report the first synthesis of lipoxazolidinone A, 15 structural analogs to explore its active pharmacophore, and initial resistance and mechanism of action studies. These results suggest that 4-oxazolidinones are valuable scaffolds for antimicrobial development and reveal simplified lead compounds for further optimization.

Copper-catalyzed Convenient Synthesis and SAR Studies of Substituted-1,2,3-triazole as Antimicrobial Agents

2018 ◽  
Vol 16 (1) ◽  
pp. 3-10
Author(s):  
Aniket P. Sarkate ◽  
Kshipra S. Karnik ◽  
Pravin S. Wakte ◽  
Ajinkya P. Sarkate ◽  
Ashwini V. Izankar ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antifungal Activity ◽  
Antimicrobial Agents ◽  
Cycloaddition Reaction ◽  
Dipolar Cycloaddition ◽  
One Pot ◽  
Triazole Derivatives ◽  
Sar Studies ◽  
Convenient Synthesis ◽  
Antibacterial And Antifungal

Background:A novel copper-catalyzed synthesis of substituted-1,2,3-triazole derivatives has been developed and performed by Huisgen 1,3-dipolar cycloaddition reaction of azides with alkynes. The reaction is one-pot multicomponent.Objective:We state the advancement and execution of a methodology allowing for the synthesis of some new substituted 1,2,3-triazole analogues with antimicrobial activity.Methods:A series of triazole derivatives was synthesized by Huisgen 1,3-dipolar cycloaddition reaction of azides with alkynes. The structures of the synthesized compounds were elucidated and confirmed by 1H NMR, IR, MS and elemental analysis. All the synthesized compounds were tested for their antimicrobial activity against a series of strains of Bacillus subtilis, Staphylococcus aureus and Escherichia coli for antibacterial activity and against the strains of Candida albicans, Aspergillus flavus and Aspergillus nigar for antifungal activity, respectively.Results and Conclusion:From the antimicrobial data, it was observed that all the newly synthesized compounds showed good to moderate level of antibacterial and antifungal activity.

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