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

Abstract

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.

A Click Chemistry Approach to Tetrazoles: Recent Advances

“…Very recently, Jonnalagadda et al have synthesized some tetrazole-linked benzochromene derivatives and had their molecular docking study as well [76]. 5-Substituted 5-styryl terazolo [1,5-c]quinazoline derivatives were studied for their cytotoxicity and molecular docking by Parbhoo et al [77]. In a similar fashion, several tetrazole derivatives were synthesized and subject to molecular docking in recent years [78][79][80][81][82].…”

β-Cyclodextrin-Based Nanosponges Inclusion Compounds Associated with Gold Nanorods for Potential NIR-II Drug Delivery

“…In recent decades, curcumin (CUR) has received increasing attention due to its biofunctional properties [ 22 , 23 , 24 , 25 ]. On the other hand, melphalan (4-[bis(2-chloroethyl)amino] -L-phenylalanine) is a derivative of nitrogen mustard with antineoplastic activity [ 18 , 26 , 27 ].…”

Synthesis, characterization, and anticancer activity of some azole‐heterocyclic complexes with gold(III), palladium(II), nickel(II), and copper(II) metal ions

“…Tetrazole and its derivatives, on the other hand, exhibit a wide variety of biological properties including antibacterial, antimicrobial, anti‐inflammatory, antifungal, antiviral, antinociceptive, analgesic, cyclo‐oxygenase inhibition, and anticancer activities . Tetrazole derivatives exhibited anticancer activity against Hep G2, A 549, DU 145, and MCF‐7 cell lines …”

“…[3] Tetrazole derivatives exhibited anticancer activity against Hep G2, [3,15] A 549, DU 145, [15] and MCF-7 cell lines. [16,17] Metal complexes of substituted tetrazoles have been of interest lately to pharmaceutical investigators because of their ability to act as antitumor agents [18] These complexes can exhibit several modes of coordination. They may bond as unidentate form through the N1 or the N2 position of the tetrazole ring or they can act as a bidentate ligand.…”