Photochemical synthesis, intercalation with DNA and antitumor evaluation in vitro of benzo[d]thiazolo[3,2-a]quinolin-10-ium derivatives

Alina E Saifutiarova; Yuri V Fedorov; Vladimir B Tsvetkov; Dina A Rustamova; Elena N Gulakova; Nelly S Chmelyuk; Maxim A Abakumov; Teimur M Aliev; Olga A Fedorova

doi:10.1016/j.bioorg.2021.105267

Photochemical synthesis, intercalation with DNA and antitumor evaluation in vitro of benzo[d]thiazolo[3,2-a]quinolin-10-ium derivatives

Bioorg Chem. 2021 Oct:115:105267. doi: 10.1016/j.bioorg.2021.105267. Epub 2021 Aug 16.

Authors

Alina E Saifutiarova¹, Yuri V Fedorov², Vladimir B Tsvetkov³, Dina A Rustamova⁴, Elena N Gulakova², Nelly S Chmelyuk⁵, Maxim A Abakumov⁶, Teimur M Aliev², Olga A Fedorova⁷

Affiliations

¹ A. N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences, 119991, Vavilova str., 28, Moscow, Russia; D. Mendeleev University of Chemical Technology of Russia, 125047, Miusskaya sqr. 9, Moscow, Russia. Electronic address: baykova.alina@gmail.com.
² A. N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences, 119991, Vavilova str., 28, Moscow, Russia.
³ WCRC "Digital biodesign and personalized healthcare", Sechenov First Moscow State Medical University, 8/2 Trubetskaya Str., Moscow 119146, Russia. Electronic address: v.b.tsvetkov@gmail.com.
⁴ D. Mendeleev University of Chemical Technology of Russia, 125047, Miusskaya sqr. 9, Moscow, Russia.
⁵ Laboratory "Biomedical Nanomaterials", National University of Science and Technology "MISiS", Leninskiy Prospect, 4, 119049 Moscow, Russia.
⁶ Laboratory "Biomedical Nanomaterials", National University of Science and Technology "MISiS", Leninskiy Prospect, 4, 119049 Moscow, Russia; Department of Medical Nanobiotechnoilogy, Pirogov Russian National Research Medical University, Ostrovityanova str., 1, 117997 Moscow, Russia.
⁷ A. N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences, 119991, Vavilova str., 28, Moscow, Russia; D. Mendeleev University of Chemical Technology of Russia, 125047, Miusskaya sqr. 9, Moscow, Russia.

PMID: 34426158
DOI: 10.1016/j.bioorg.2021.105267

Abstract

A new anticancer benzo[d]thiazolo[3,2-a]quinolin-10-ium derivatives were synthesized and characterized. Anticancer evaluation in vitro against four cancer cell lines including adenocarcinomic human alveolar basal epithelial cells (A549), hepatocellular carcinoma (HepG2), prostate cancer (PC3) and breast cancer (MCF7) indicated that some of prepared compounds shows higher selectivity in comparison with doxorubicin. DNA interaction studies by optical, CD, NMR spectroscopies showed the high affinity of benzothiazole ligands towards the dsDNA. The ligand-DNA interaction occurs through the intercalation of benzo[d]thiazolo[3,2-a]quinolin-10-ium derivatives with nucleic acid. The investigation of formed ligand - DNA complexes by docking and molecular dynamic calculations was applied for analysis of the relationship between structure and anticancer activity. The results suggested that benzo[d]thiazolo[3,2-a]quinolin-10-ium derivatives might serve as a novel scaffold for the future development to new antitumor agents.

Keywords: Anticancer agent; Complex formation; DNA; Intercalation; Photochemical synthesis; Styryl dye.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Benzothiazoles / chemical synthesis
Benzothiazoles / chemistry
Benzothiazoles / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
DNA / chemistry*
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Models, Molecular
Molecular Structure
Photochemical Processes
Quinolinium Compounds / chemical synthesis
Quinolinium Compounds / chemistry
Quinolinium Compounds / pharmacology*
Structure-Activity Relationship

Substances

Antineoplastic Agents
Benzothiazoles
Quinolinium Compounds
DNA
benzothiazole