Background: 1,2,3–Triazolyl–tetrazoles have received substantial attention because of its unique bioisosteric properties and extraordinarily broad spectrum of biological activity, making them interesting for the drug design and synthesis of delightful class of widely investigated heterocyclic compounds. To address major health concerns, it is consequently important to devote ongoing effort for the identification and development of New Chemical Entities (NCEs) as possible anticancer medicines. Methods: We began our initial investigation of the reaction between 5-(azidomethyl)-1H-pyrrolo[2,3-b]pyridine, 1-phenylsubstituted-5-(prop-2-yn-1-ylthio)-1H-tetrazole under click chemistry to gave the corresponding triazole precursors and screened for their cytotoxicity reported by variations in therapeutic actions of parent molecule. All of the prepared scaffolds were characterised by proton, carbon resonance spectroscopy, IR, and mass spectral techniques. Results: When tested for in vitro antitumor activity that the prepared compounds 7e, 7h had a significant anticancer activity against human adenocarcinoma Hs766T cell line with IC50 = 5.33, 4.92 μg/mL and Hs460 cell line with IC50 = 4.82, 6.15 μg/mL respectively. Final scaffolds 7f, 7h, 7j acquiring highest potential drug binding scores ΔG = –10.42, –8.80, –9.37 Kcal/, with amino acids residues Ala A:11 (2.195 A˚), Asp A:119 (1.991 A˚), Thr A:58 (1.890 A˚), Lys A:16 (1.253 A˚), Asp A:38 (2.013 A˚), Lys A:117 (2.046 A˚) respectively and processing Lipinski’s rule of five as good oral bioavailability agents. Conclusion: The molecular framework for the synthesis of novel azaindole 1,2,3–triazole scaffolds coupled to tetrazole core was discovered in our study and evaluation of anticancer activity.
Background and objective: A study on the chemical and biological properties of molecules simultaneously comprising various heterocycles, such as fused 1,3,4–oxadiazole and 1,2,3–triazoles, has been conducted as part of our ongoing research in the field of medicinal and organic chemistry. In the present study, novel 1,3,4-oxadiazoles and 1,2,3-triazoles incorporating a phthalazine ring have been synthesized and evaluated for their anticancer activity and docking analysis. Methods: In this study, we performed ligand–based pharmacophore modeling as a promising design strategy of substituted phthalazin–1(2H)–one–1,3,4–oxadiazole acetamides (4); 1,2,3–triazole–1,3,4–oxadiazolyl)phthalazin-1(2H)-one (5) were synthesized from key intermediate 2-((5-mercapto-1,3,4-oxadiazol-2-yl)methyl)-4-methylphthalazin-1(2H)-one 2. The prepared compounds were characterized by proton and carbon nuclear magnetic resonance spectroscopy, infrared, elemental analysis, and mass spectroscopy. Synthesized scaffolds were screened for their anticancer activity against three cell lines, MCF-7, T-47D, and MDA-MB-231, by MTT assay. The prepared ligands were docked by using the input protocols, like RCSB, AutoDock 4.2, ACD ChemSketch, Open Babel, and SwissADME. Results: The final compound 5f exhibited excellent activity (IC50 = 10.21 ± 2.2, 7.53 ± 0.1 µM) against T-47D and MCF-7 cancer cell lines, respectively, and compounds 4b and 5b showed the highest % growth of inhibition (61.25 ± 0.52, 62.48 ± 0.20 µg/mL) against T-47D and MCF-7 cell lines, which has been found to be equivalent to that reported by the standard cisplatin. The prepared ligand 5f exhibited greatest bonding with amino acids AlaX:191, MetX:193, ValX:196, ThrX:140, PheX:192, TyrX:155, AsnX:90, LysX:159, LeuX:95, and IleX:14, with a docking score of –11.53 Kcal/mol, respectively. These compounds were further evaluated for their ADMET and physicochemical properties by using SwissADME. Conclusion: Phthalazine with 1,3,4–oxadiazole substituents and 1,2,3–triazoles containing 1,3,4–oxadiazole ring displayed excellent anticancer activity; some interesting relationship has also been evidenced between the synthesised structures and their antimicrobial activity and docking studies. In light of all the above findings, it can be concluded that these molecules may serve as lead molecules for further synthetic and biological evaluation.
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