Synthesis and Biological Evaluation of Phaeosphaeride A Derivatives as Antitumor Agents

Victoria Abzianidze; Petr Beltyukov; Sofya Zakharenkova; Natalia Moiseeva; Jennifer Mejia; Alvin Holder; Yuri Trishin; Alexander Berestetskiy; Victor Kuznetsov

doi:10.3390/molecules23113043

Synthesis and Biological Evaluation of Phaeosphaeride A Derivatives as Antitumor Agents

Molecules. 2018 Nov 21;23(11):3043. doi: 10.3390/molecules23113043.

Authors

Victoria Abzianidze¹, Petr Beltyukov², Sofya Zakharenkova³, Natalia Moiseeva⁴, Jennifer Mejia⁵, Alvin Holder⁶, Yuri Trishin⁷, Alexander Berestetskiy⁸, Victor Kuznetsov⁹

Affiliations

¹ Laboratory of Chemical Modeling, Research Institute of Hygiene, Occupational Pathology and Human Ecology, Federal Medical Biological Agency, p/o Kuz'molovsky, 188663 Saint Petersburg, Russia. vvaavv@mail.ru.
² Laboratory of Molecular Toxicology and Experimental Therapy, Research Institute of Hygiene, Occupational Pathology and Human Ecology, Federal Medical Biological Agency, p/o Kuz'molovsky, 188663 Saint Petersburg, Russia. biochem2005@rambler.ru.
³ Laboratory of Chemical Modeling, Research Institute of Hygiene, Occupational Pathology and Human Ecology, Federal Medical Biological Agency, p/o Kuz'molovsky, 188663 Saint Petersburg, Russia. sofya.zakharenkova@gmail.com.
⁴ N.N. Blokchin National Medical Research Center of Oncology, 115478 Moscow, Russia. n.i.moiseeva@gmail.com.
⁵ Department of Chemistry and Biochemistry, Old Dominion University, 4541 Hampton Boulevard, Norfolk, VA 23529, USA. jmatt024@odu.edu.
⁶ Department of Chemistry and Biochemistry, Old Dominion University, 4541 Hampton Boulevard, Norfolk, VA 23529, USA. aholder@odu.edu.
⁷ Saint Petersburg State University of industrial technologies and design, Ivana Chernyh str., 4, 198095 Saint Petersburg, Russia. trish@yt4470.spb.edu.
⁸ All-Russian Institute of Plant Protection, Russian Academy of Agricultural Sciences, Pushkin, 196608 Saint Petersburg, Russia. aberestetski@yahoo.com.
⁹ Laboratory of Chemical Modeling, Research Institute of Hygiene, Occupational Pathology and Human Ecology, Federal Medical Biological Agency, p/o Kuz'molovsky, 188663 Saint Petersburg, Russia. kuznetsov_va1956@bk.ru.

Abstract

New derivatives of phaeosphaeride A (PPA) were synthesized and characterized. Anti-tumor activity studies were carried out on the HCT-116, PC3, MCF-7, A549, К562, NCI-Н929, Jurkat, THP-1, RPMI8228 tumor cell lines, and on the HEF cell line. All of the compounds synthesized were found to have better efficacy than PPA towards the tumor cell lines mentioned. Compound 6 was potent against six cancer cell lines, HCT-116, PC-3, K562, NCI-H929, Jurkat, and RPMI8226, showing a 47, 13.5, 16, 4, 1.5, and 7-fold increase in anticancer activity comparative to those of etoposide, respectively. Compound 1 possessed selectivity toward the NCI-H929 cell line (IC₅₀ = 1.35 ± 0.69 μM), while product 7 was selective against three cancer cell lines, HCT-116, MCF-7, and NCI-H929, each having IC₅₀ values of 1.65 μM, 1.80 μM and 2.00 μM, respectively.

Keywords: HEF cell line; acute toxicity; antitumor activity; human tumor cell lines; natural phaeosphaeride A.

MeSH terms

A549 Cells
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis*
Bridged Bicyclo Compounds, Heterocyclic / chemistry
Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
Drug Screening Assays, Antitumor
HCT116 Cells
Humans
Jurkat Cells
MCF-7 Cells
Molecular Structure
Structure-Activity Relationship

Substances

Antineoplastic Agents
Bridged Bicyclo Compounds, Heterocyclic
phaeosphaeride A