Light-driven photoswitching of quinazoline analogues of combretastatin A-4 as an effective approach for targeting skin cancer cells

• Published in: Organic & biomolecular chemistry Vol. 19; no. 35; pp. 767 - 7677
• Main Authors: Scherbakov, A. M, Balakhonov, R. Yu, Salnikova, D. I, Sorokin, D. V, Yadykov, A. V, Markosyan, A. I, Shirinian, V. Z
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 15.09.2021; Royal Society of Chemistry
• Subjects: 5-Fluorouracil; Antiproliferatives; Apoptosis; Cancer; Cell death; Chemistry; Chemistry, Organic; Chemotherapy; Cisplatin; Irradiation; NMR; Nuclear magnetic resonance; Photochemicals; Photodegradation; Physical Sciences; Science & Technology; Skin cancer; Sunlight; Z-form; MEDICINAL CHEMISTRY; BIOLOGICAL EVALUATION; AGENTS; CLEAVAGE; TUBULIN; ANTI-MONOAMINE OXIDASE; A4 PHOSPHATE; DERIVATIVES; ANTITUMOR; PHOTOCHEMICAL-REARRANGEMENT
• ISSN: 1477-0520; 1477-0539; 1477-0539
• DOI: 10.1039/d1ob01362a

A novel quinazoline series of photoswitchable combretastatin A-4 (CA-4) analogues were synthesized and their photochemical properties and antiproliferative activity against A431 epidermoid carcinoma cells were studied. It was found that quinazoline analogues, in contrast to the majority of the known CA-4, exhibit high antiproliferative activity in the E -form as well. Photoswitching of the E -form to the Z -form resulted in a multiple (9-fold) increase in antiproliferative activity. 1 H NMR monitoring showed that these compounds are very resistant to UV ( λ = 365 nm) or sunlight irradiation and do not undergo photodegradation with a loss of antiproliferative activity that is inherent in heterocyclic analogues of CA-4. Similar photoswitching and an increase in antiproliferative activity are observed on exposure to sunlight. A selected compound ( 1a -Z51) in sub-micromolar concentrations induced apoptosis in A431 cells, while rad50/ATM/p53 were not involved in cell death. The growth of A431 cells was significantly inhibited after combination treatment with compound 1a -Z51 and chemotherapy drugs (cisplatin or 5-fluorouracil). In summary, the quinazoline analogues of CA-4 represent a promising strategy to achieve a photoswitchable potency for the treatment of cancers, including the development of combination therapies. A study of the photochemical properties and antiproliferative activity of new quinazoline analogues of combretastatin A-4 found that irradiation with UV or sunlight leads to a significant increase in activity towards epidermoid carcinoma cells.