Synthesis and Evaluation of Biological Activity of Homodrimane Sesquiterpenoids Bearing 1,3,4-Oxadiazole or 1,3,4-Thiadiazole Units

Lungu, Lidia; Ciocârlan, Alexandru; Smigon, Crina; Özer, Işıl; Shova, Sergiu; Gutu, Iacob; Vornicu, Nicoleta; Mangalagiu, Ionel I.; D’Ambrosio, Michele; Aricu, Aculina

doi:10.1007/s10593-020-02703-7

Cited by 11 publications

(3 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Taking into consideration the above considerations and our expertise in the field of antibacterial and antifungal agents [ 13 , 15 , 20 , 21 , 22 , 23 , 24 , 25 ], we report here the design, synthesis, molecular docking, antibacterial and antifungal evaluation of some new benzo[f]quinoline derivatives.…”

Section: Introductionmentioning

confidence: 99%

Benzoquinoline Derivatives: A Straightforward and Efficient Route to Antibacterial and Antifungal Agents

et al. 2021

View full text Add to dashboard Cite

We report here the design, synthesis, experimental and in silico evaluation of the antibacterial and antifungal activity of some new benzo[f]quinoline derivatives. Two classes of benzo[f]quinolinium derivatives—(benzo[f]quinolinium salts (BQS) and pyrrolobenzo[f]quinolinium cycloadducts (PBQC)—were designed and obtained in two steps via a direct and facile procedure: quaternization followed by a cycloaddition reaction. The synthesized compounds were characterized by elemental and spectral analysis (FT-IR, 1H-NMR, 13C-NMR). The antimicrobial assay reveals that the BQS salts have an excellent quasi-nonselective antifungal activity against the fungus Candida albicans (some of them higher that the control drug nystatin) and very good antibacterial activity against the Gram positive bacterium Staphylococcus aureus. The PBQC compounds are inactive. Analysis of the biological data reveals interesting SAR correlations in the benzo[f]quinolinium series of compounds. The in silico studies furnished important data concerning the pharmacodynamics, pharmacokinetics and ADMET parameters of the BQS salts. Studies of the interaction of each BQS salt 3a–o with ATP synthase in the formed complex, reveal that salts 3j, 3i, and 3n have the best fit in a complex with ATP synthase. Study of the interaction of each BQS salt 3a-o with TOPO II in the formed complex reveals that salts 3j and 3n have the best-fit in complex with TOPO II. The in silico ADMET studies reveal that the BQS salts have excellent drug-like properties, including a low toxicity profile. Overall, the experimental and in silico studies indicate that compounds 3e and 3f (from the aliphatic series), respectively, and 3i, 3j and 3n (from the aromatic series), are promising leading drug candidates.

show abstract

Section: Introductionmentioning

confidence: 99%

Benzoquinoline Derivatives: A Straightforward and Efficient Route to Antibacterial and Antifungal Agents

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The synthesis of terpene—heterocyclic compounds has seen a vertiginous development in the last 10 years. A great number of molecular hybrids containing a terpene unit and one of the following heterocycles: diazine [ 11 , 12 ], 1,2,4-triazole and carbazole [ 13 , 14 ], azaheterocyclic [ 15 , 16 ], hydrazinecarbothioamide and 1,2,4-triazole [ 17 ], 1,3,4-oxadiazole and 1,3,4-thiadiazole [ 18 ], thiosemicarbazone and 1,3-thiazole [ 19 ], or benzothiazole [ 20 ], many of which showed excellent antifungal and/or antibacterial activity, were reported elsewhere.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Antimicrobial Activity Evaluation of Homodrimane Sesquiterpenoids with a Benzimidazole Unit

et al. 2023

Self Cite

View full text Add to dashboard Cite

Herein we report a feasible study concerning the synthesis and the in vitro antimicrobial activity of some new homodrimane sesquiterpenoids with a benzimidazole unit. Based on some homodrimane carboxylic acids, on their acyl chlorides and intermediate monoamides, a series of seven N-homodrimenoyl-2-amino-1,3-benzimidazoles and 2-homodrimenyl-1,3-benzimidazoles was synthesized. The syntheses involved the decarboxylative cyclization and condensation of the said acids or acyl chlorides with o-phenylendiamine and 2-aminobenzimidazole, as well as the p-TsOH-mediated cyclodehydration of the said monoacylamides. The structures of the synthesized compounds have been fully confirmed, including by the X-ray diffraction. Their biological activities were evaluated on five species of fungi (Aspergillus niger, Fusarium solani, Penicillium chrysogenum, P. frequentans, and Alternaria alternata) and two strains of bacteria (Bacillus sp. and Pseudomonas aeruginosa). Compounds 7 and 20 showed higher antifungal (MIC = 0.064 and 0.05 μg/mL) and antibacterial (MIC = 0.05 and 0.032 μg/mL) activities compared to those of the standards: caspofungin (MIC = 0.32 μg/mL) and kanamycin (MIC = 2.0 μg/mL), and compounds 4, 10, 14, and 19 had moderate activities.

show abstract

“…Antibioticresistant cells develop as a result of biofilm, which decreases the spread of standard antibiotics [40]. By changing the target enzymes, lessening the cell's permeability to prevent On the other hand, 1,3,4-thiadiazoles [8][9][10][11][12][13][14][15][16][17] and their analogies have revealed a wide variety of effects, such as antiviral, anti-inflammatory, antidiabetic, anticancer, antimicrobial, and anticonvulsant ones, in biomedical and pharmaceutical applications [18,19]. Moreover, pyrimidines and their hybrid molecules are considered to be a favorable research area for medicinal chemists [20][21][22][23][24][25][26][27][28][29][30] owing to their richness in both synthetic and natural bioactive molecules along with various involvement in polymers, biopolymers, and pharmaceuticals, and they can act as ligands.…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial Potency and E. coli β-Carbonic Anhydrase Inhibition Efficacy of Phenazone-Based Molecules

Rashdan,

El-Sayyad,

Shehadi

et al. 2023

Molecules

View full text Add to dashboard Cite

In this investigation, 4-antipyrinecarboxaldhyde was reacted with methyl hydrazinecarbodithioate to afford the carbodithioate derivative 3. The as-prepared carbodithioate derivative 3 is considered to be a key molecule for the preparation of new antipyrine-1,3,4-thiadiazole-based molecules (4–9) through its reaction with the appropriate hydrazonoyl halides. Furthermore, a typical Biginelli three-component cyclocondensation reaction involving ethyl acetoacetate, 4-antipyrinecarboxaldhyde, and thiourea under the standard conditions is carried out in the presence of sulfuric acid to afford the corresponding antipyrine–pyrimidine hybrid molecule (10). The latter was submitted to react with hydrazine monohydrate to provide the corresponding hydrazide derivative (11) which, under reaction with ethyl acetoacetate in refluxing ethanol containing catalytic amount of acetic acid, afforded the corresponding derivative (12). The structure of the newly synthesized compounds was affirmed by their spectral and microanalytical data. We also screened for their antimicrobial potential (ZOI and MIC) and conducted a kinetic study. Additionally, the mechanism of biological action was assessed by a membrane leakage assay and SEM imaging technique. Moreover, the biological activities and the binding modes of these compounds were further supplemented by an in silico docking study against E. coli β-carbonic anhydrase. The amount of cellular protein released by E. coli is directly correlated to the concentration of compound 9, which was found to be 177.99 µg/mL following treatment with 1.0 mg/mL of compound 9. This finding supports compound 9’s antibacterial properties and explains how the formation of holes in the E. coli cell membrane results in the release of proteins from the cytoplasm. The newly synthesized compounds represent acceptable antimicrobial activities with potential action against E. coli β-carbonic anhydrase. The docking studies and antimicrobial activity test proved that compound (9) declared a greater activity than the other synthesized compounds.

show abstract

Synthesis and Evaluation of Biological Activity of Homodrimane Sesquiterpenoids Bearing 1,3,4-Oxadiazole or 1,3,4-Thiadiazole Units

Cited by 11 publications

References 23 publications

Benzoquinoline Derivatives: A Straightforward and Efficient Route to Antibacterial and Antifungal Agents

Benzoquinoline Derivatives: A Straightforward and Efficient Route to Antibacterial and Antifungal Agents

Synthesis and Antimicrobial Activity Evaluation of Homodrimane Sesquiterpenoids with a Benzimidazole Unit

Antimicrobial Potency and E. coli β-Carbonic Anhydrase Inhibition Efficacy of Phenazone-Based Molecules

Contact Info

Product

Resources

About