Synthesis, Cytotoxicity and Molecular Docking Studies of the 9-Substituted 5-Styryltetrazolo[1,5-c]quinazoline Derivatives
| Autor: | Nishal Parbhoo, Malose J. Mphahlele, Samantha Gildenhuys |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Stereochemistry
Cell Survival Protein Data Bank (RCSB PDB) Substituent Molecular Conformation Pharmaceutical Science Antineoplastic Agents Chemistry Techniques Synthetic Conjugated system 010402 general chemistry 01 natural sciences Article Analytical Chemistry lcsh:QD241-441 HeLa 9-bromo-5-styryltetrazolo[1 5-c]quinazoline cross-coupling 9-carbo–substituted 5-styryltetrazolo[1 5-c]quinazolines cytotoxicity molecular docking chemistry.chemical_compound Structure-Activity Relationship lcsh:Organic chemistry Cell Line Tumor Drug Discovery Quinazoline Humans Physical and Theoretical Chemistry Cytotoxicity Cell Proliferation biology Molecular Structure 010405 organic chemistry Chemistry Hydrogen bond Organic Chemistry biology.organism_classification Combinatorial chemistry 0104 chemical sciences Molecular Docking Simulation Tubulin Chemistry (miscellaneous) biology.protein Quinazolines Molecular Medicine |
| Zdroj: | Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry Molecules; Volume 22; Issue 11; Pages: 1719 Molecules, Vol 22, Iss 11, p 1719 (2017) |
| ISSN: | 1420-3049 |
| Popis: | In this paper, we describe the synthesis of the 5-styryltetrazolo[1,5-c]quinazolines substituted at the 9-position with a 4-fluorophenyl ring directly or via a conjugated π-spacer (C=C or C≡C bond) based on the 6-bromo-4-chloro-2-styrylquinazoline scaffold. The structures of the synthesized compounds were characterized based on a combination of 1H-NMR, 13C-NMR, IR and high resolution mass spectral data as well as microanalyses. The tetrazoloquinazolines were evaluated for potential in vitro cytotoxicity against the human breast adenocarcinoma (MCF-7) and cervical cancer (HeLa) cells. The anti-proliferative assays demonstrated that the 9-bromo-5-styryltetrazolo[1,5-c]quinazoline 3a and 9-bromo-5-(4-fluorostyryl)tetrazolo[1,5-c]quinazoline 3b exhibit significant cytotoxicity against both cell lines. A carbon-based substituent at the 9-position resulted in complete loss of cytotoxicity against both cell lines except for the 5,9-bis((E)-4-fluorostyryl)tetrazolo[1,5-c]quinazoline 4e, which was found to exhibit comparable cytotoxicity to that of Melphalan (IC50 = 61 μM) against the MCF-7 cell line with IC50 value of 62 μM. Molecular docking against tubulin (PDB:1TUB) showed that compounds 3a, 3b and 4e bind to the tubulin heterodimer. Binding involves hydrogen bonding for 3a and 3b and halogen interactions for 4e. |
| Databáze: | OpenAIRE |
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