Synthesis and Rational Design of New Appended 1,2,3-Triazole-uracil Ensembles as Promising Anti-Tumor Agents via In Silico VEGFR-2 Transferase Inhibition

• Published in: Molecules (Basel, Switzerland) Switzerland), 2021-03, Vol.26 (7), p.1952
• Main Authors: Reddy, Nadipolla Naresh, Hung, Sung-Jen, Swamy, Merugu Kumara, Sanjeev, Ananthula, Rao, Vankadari Srinivasa, Rohini, Rondla, Raju, Atcha Krishnam, Bhaskar, Kuthati, Hu, Anren, Reddy, Puchakayala Muralidhar
• Format: Article
• Language: English
• Subjects: 1,2,3-triazole-uracil; 5-Fluorouracil; Amino acids; Angiogenesis; Animals; anti-cancer agents; Antifungal agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Azide; Cancer; Cell Proliferation - drug effects; Chemical reactions; Chemotherapy; Cytotoxicity; Dose-Response Relationship, Drug; Drug Design; Drug development; Drug Screening Assays, Antitumor; HeLa Cells; Humans; Hydrogen bonds; in silico docking; Ligands; Mass spectrometry; Mass spectroscopy; Mice; Molecular Structure; MTT assay; NIH 3T3 Cells; NMR; Nuclear magnetic resonance; Protein Binding; Protein Kinase Inhibitors - chemical synthesis; Protein Kinase Inhibitors - pharmacology; Proteins; Structure-Activity Relationship; Toxicity testing; Triazoles; Triazoles - chemistry; Tumor cells; Uracil; Uracil - chemistry; Vascular Endothelial Growth Factor Receptor-2 - antagonists & inhibitors; Vascular endothelial growth factor receptors; VEGFR-2
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26071952

Angiogenesis inhibition is a key step towards the designing of new chemotherapeutic agents. In a view to preparing new molecular entities for cancer treatment, eighteen 1,2,3-triazole-uracil ensembles - were designed and synthesized via the click reaction. The ligands were well characterized using H-, C-NMR, elemental analysis and ESI-mass spectrometry. The in silico binding propinquities of the ligands were studied sequentially in the active region of VEGFR-2 using the Molegro virtual docker. All the compounds produced remarkable interactions and potentially inhibitory ligands against VEGFR-2 were obtained with high negative binding energies. Drug-likeness was assessed from the ADME properties. Cytotoxicity of the test compounds was measured against HeLa and HUH-7 tumor cells and NIH/3T3 normal cells by MTT assay. Compound showed higher growth inhibition activity than the positive control, 5-fluorouracil (5-FU), against both HeLa and HUH-7 cells with IC values of 4.5 and 7.7 μM respectively. Interestingly, the compounds - did not show any cytotoxicity towards the normal cell lines. The results advance the position of substituted triazoles in the area of drug design with no ambiguity.