Synthesis, Cytotoxicity and Molecular Docking Studies of the 9-Substituted 5-Styryltetrazolo[1,5-c]quinazoline Derivatives

• Published in: Molecules (Basel, Switzerland) Switzerland), 2017-10, Vol.22 (11), p.1719
• Main Authors: Mphahlele, Malose J, Gildenhuys, Samantha, Parbhoo, Nishal
• Format: Article
• Language: English
• Subjects: 9-bromo-5-styryltetrazolo[1,5-c]quinazoline; 9-carbo–substituted 5-styryltetrazolo[1,5-c]quinazolines; Adenocarcinoma; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Cervical cancer; Cervix; Chemical bonds; Chemistry Techniques, Synthetic; cross-coupling; Cytotoxicity; Humans; Hydrogen bonding; Melphalan; Molecular Conformation; Molecular docking; Molecular Docking Simulation; Molecular Structure; Quinazolines - chemical synthesis; Quinazolines - chemistry; Quinazolines - pharmacology; Spacer; Structure-Activity Relationship; Substitutes; Tubulin
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules22111719

In this paper, we describe the synthesis of the 5-styryltetrazolo[1,5- ]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, C-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- ]quinazoline and 9-bromo-5-(4-fluorostyryl)tetrazolo[1,5- ]quinazoline 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(( )-4-fluorostyryl)tetrazolo[1,5- ]quinazoline , which was found to exhibit comparable cytotoxicity to that of Melphalan (IC = 61 μM) against the MCF-7 cell line with IC value of 62 μM. Molecular docking against tubulin (PDB:1TUB) showed that compounds , and bind to the tubulin heterodimer. Binding involves hydrogen bonding for and and halogen interactions for .