Tyrosinase-mediated synthesis of larvicidal active 1,5-diphenyl pent-4-en-1-one derivatives against Culex quinquefasciatus and investigation of their ichthyotoxicity.

1,5-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.

Green catalyst Cu(II)-enzyme-mediated eco-friendly synthesis of 2-pyrimidinamines as potential larvicides against Culex quinquefasciatus mosquito and toxicity investigation against non-target aquatic species.

Novel one-pot multicomponent synthesis of 2-pyrimidinamine derivatives can be achieved via green chemistry, using Cu(II)-tyrosinase enzyme (Cu-Tyr) as a catalyst. This method offers mild reaction conditions and a high yield of derivatives. We synthesised several compounds in this manner and evaluated their larvicidal, and antifeedant activities. Out of the synthesised derivatives, compound 3, with a median lethal dose (LD50) of 21.43 µg/mL, was highly active against Culex quinquefasciatus, compared to compounds 1a-m and 2, and the control, hydantocidin. Compounds 1j, 1d, and 1e were low active against C. quinquefasciatus with LD50 values of 78.46, 78.59, and 79.54 µg/mL, respectively. In antifeedant screening, compounds 1j, 1l, and 2 generated 100% mortality within 24 h against Oreochromis mossambicus at 100 µg/mL, where toxicity was determined as the ratio of the number of dead and live fingerlings (%) at 24 h. In contrast, compounds 1a-f, 1i, 1m, and 3 were less toxic to O. mossambicus as compared to the control, dibromoisophakellin. Therefore, compound 3 had high larvicidal activity against C. quinquefasciatus and was less toxic to non-target aquatic species. Molecular docking studies also supported the finding that compound 3 was an effective larvicide with more inhibition ability than the control hydantocidin (-9.6 vs. -6.1 kcal/mol).

Synthesis of novel coumarin analogues: Investigation of molecular docking interaction of SARS-CoV-2 proteins with natural and synthetic coumarin analogues and their pharmacokinetics studies.

The severe acute respiratory syndrome coronavirus, identified as SARS-CoV-2, initially established in Wuhan, China at the end of 2019, affects respiratory infections known as COVID-19. In an extraordinary manner, COVID-19 is affecting human life and has transformed a global public health issue into a crisis. Natural products are already recognized owing to the massive advantageous window and efficient antioxidant, antiviral immunomodulatory, and anti-inflammatory belongings. Additionally, the object of the present study was to demonstrate the inhibitory potential of the natural products coumarins and its analogues alongside SARS coronavirus. The present work, focuses on the synthesis of new coumarin analogues and characterized by FT-IR, 1H and 13C NMR, elemental analyses, and mass spectra. The recently synthesised compounds were projected conceptual association for COVID-19 protease and also to explore in anticipation if this protein will help target protease inhibitor drugs such as Calanolide A, Cardatolide A, Collinin, Inophyllum A, Mesuol, Isomesuol, Pteryxin, Rutamarin, Seselin and Suksdorin. The natural coumarin analogues docking scores were compared to standard Hydroxychloroquine. While the 3D module of SARS coronavirus main protease was predicted with the SWISS MODEL web server, as well as biochemical interaction tests were performed with the AutoDock Vina tool between the target protein with ligands. This research further showed that all the protease inhibitors accessed the target protein with negative dock energy. Molecular docking studies found that the natural coumarin analogue Inophyllum A showed an exceptional potential for inhibition with a binding energy of -8.4 kcal/mol. The synthetic coumarin analogues 1m and 1p both demonstrated a similar binding energy, inhibition potential of -7.9 kcal / mol as opposed to hydroxychloroquine and co-crystallized ligand alpha-ketoamide with binding energy values of -5.8 and -6.6 kcal / mol. All compounds evaluated were known as drug-like in nature, passing Lipinski's "Law of 5" with 0 violations except for alpha-ketoamide, passing Lipinski's "Rule of 5" with 1 violation (MW > 500). The inhibitor binding in silico research thus offers a structural understanding of COVID-19 and molecular interactions across the known protease inhibitors centred on the findings of the multiple sequence alliance.

Synthesis, Cytotoxic Analysis, and Molecular Docking Studies of Tetrazole Derivatives via N-Mannich Base Condensation as Potential Antimicrobials.

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, 1H NMR, and 13C 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.