ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Interaction between GW2974 and telomeric G-quadruplex DNA: a possible anticancer mechanism

Ismail A. Elhaty

Department of Nutrition and Dietetics, Faculty of Health Sciences, Istanbul Gelisim University, Istanbul, Turkey

E-mail: iaeismail@gelisim.edu.tr

Received: 21 April 2021  Accepted: 19 July 2021

Abstract:

Human telomere consists of tandem repeats of guanines; thus, it can form an intramolecular G-quadruplex structure, which can inhibit the telomerase enzyme that is found active in more than 85% of cancer cells. The present work investigated the interactions of GW2974, a quinazoline derivative with telomeric G-quadruplex AG₃(TTAGGG)_3. GW2974 had shown a good affinity to G-quadruplex DNA with a binding constant of 2.41 × 10⁶ M⁻¹ and melting temperature shift ΔTm of 9.9 °C. Increasing the GW2974 ratio with DNA up to five times showed an inverse effect on G-quadruplex DNA stability. The stoichiometric ratio between GW2974 and TelQ (per strand) was 2:1. Results obtained from absorption, fluorescence, and CD spectroscopic techniques indicated that GW2974 interacted with G-quadruplex through different binding modes. GW2974 showed good specificity to quadruplex over duplex DNA by 4.71-fold. These results indicated that stabilizing of telomeric G-quadruplex inhibited telomerase enzyme, which could be a potential anticancer mechanism of GW2974.

Keywords: Telomere; Telomerase; Quadruplex; Cancer; GW2974

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-021-01801-w

Chemical Papers 75 (12) 6323–6333 (2021)