Purpose
A new series of tetrazole derivatives, which are renowned antimicrobials possessing a five-membered aromatic heterocyclic group, are synthesized herein and subjected to antimicrobial and cytotoxicity screening.
Methods
The tetrazole derivatives were synthesized via ultrasonication using Mannich base condensation. Structural verification of the products was performed using IR,
1
H NMR, and
13
C NMR spectroscopy, as well as mass spectroscopic and elemental analyses. The compounds were then screened for antimicrobial and cytotoxic activity against HepG2 (liver), MCF-7 (breast), and HeLa (cervical) cell lines. Inter- and intra-molecular binding interactions were determined using molecular docking studies. The exact binding mode between the most active tetrazole derivatives (ie, 1b, 2a, and 2b) and the proteins (ie, 4OR7, 1AI9, and 4FM9) was established using Autodock Vina 1.1.2 software and compared to the binding mode of the reference compounds (ie, cefazolin, clotrimazole, and fluorouracil).
Results
Compound 1b was extremely active against
Enterococcus faecalis
relative to the positive control cefazolin. Compounds 1b and 1e were active against
Candida albicans
and
Microsporum audouinii
compared to the positive control clotrimazole in antifungal screening. The HepG2 (liver) and MCF-7 (breast) cancer cell lines were particularly susceptible to the synthesized compounds. Compared to the control compound fluorouracil, 2a and 2b were extremely active against all three cancer cell lines. Molecular docking studies showed that 2b exhibited higher binding affinity (−7.8 kcal/mol) to the 4OR7 protein than the control cefazolin (−7.2 kcal/mol).
Conclusion
Generally, 1b, 2a, and 2b exhibited impressive inhibitory capabilities in antibacterial, antifungal, and cytotoxic screenings relative to the reference compounds. The results of the molecular docking studies and both the microbial and anticancer screenings indicate that these novel derivatives could be developed into potential therapeutic agents for medical applications.
Abstract1,5-diphenylpent-4-en-1-one derivatives were synthesised using the grindstone method with Cu(II)-tyrosinase used as a catalyst. This method showed a high yield under mild reaction conditions. The synthesised compounds were identified by FTIR, 1H NMR, 13C NMR, mass spectrometry, and elemental analysis. In this study, a total of 17 compounds (1a–1q) were synthesised, and their larvicidal and antifeedant activities were evaluated. Compound 1i (1-(5-oxo-1,5-diphenylpent-1-en-3-yl)-3-(3-phenylallylidene)thiourea) was notably more active (LD50: 28.5 µM) against Culex quinquefasciatus than permethrin(54.6 µM) and temephos(37.9 µM), whereas compound 1i at 100 µM caused 0% mortality in Oreochromis mossambicus within 24 h in an antifeedant screening, with ichthyotoxicity determined as the death ratio (%) at 24 h. Compounds 1a, 1e, 1f, 1j, and 1k were found to be highly toxic, whereas 1i was not toxic in antifeedant screening. Compound 1i was found to possess a high larvicidal activity against C. quinquefasciatus and was non-toxic to non-target aquatic species. Molecular docking studies also supported the finding that 1i is a potent larvicide with higher binding energy than the control (− 10.0 vs. − 7.6 kcal/mol) in the 3OGN protein. Lead molecules are important for their larvicidal properties and application as insecticides.
A series of 2-thioxo pyrimidine derivatives 1, (1 a-1 e) and 2, (2 a-2 e) were synthesized via Biginelli reaction by using Cu IItyrosinase (Cu II -Tyr) as an enzyme catalyst in up to 80-92% yield. The compounds 1, (1 a-1 e) and 2, (2 a-2 e) were characterized by IR, 1 H NMR, 13 C NMR, mass spectra and elemental analyses. The synthesized compounds 1, (1 a-1 e) and 2, (2 a-2 e) were screened for mosquito larvicidal activity against Culex quinquefasciatus. The compound 2 a was 80% mortality at 100 μg/mL with the LD 50 value of 55.94 μg/mL than the control Permethrin 60.03 μg/mL respectively. Molecular docking studies of synthesized compounds were carried out and the results proposed that the compound 2 a as a potential candidate to mosquito odorant-binding protein 3OGN inhibitors. In addition, computational studies, the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies showed that the charge transfer occurs in the inside of the molecule and also gives the chemical reactivity descriptors, and molecular electrostatic potential (MESP) is also calculated. Therefore, experimental and theoretical studies were well supported for the compound 2 a as a potential larvicide activity aganist mosquito larvae of Culex quinquefasciatus.
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