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
Affiliations
Victoria Abzianidze
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
Petr Beltyukov
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
Sofya Zakharenkova
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
Natalia Moiseeva
N.N. Blokchin National Medical Research Center of Oncology, 115478 Moscow, Russia
Jennifer Mejia
Department of Chemistry and Biochemistry, Old Dominion University, 4541 Hampton Boulevard, Norfolk, VA 23529, USA
Alvin Holder
Department of Chemistry and Biochemistry, Old Dominion University, 4541 Hampton Boulevard, Norfolk, VA 23529, USA
Yuri Trishin
Saint Petersburg State University of industrial technologies and design, Ivana Chernyh str., 4, 198095 Saint Petersburg, Russia
Alexander Berestetskiy
All-Russian Institute of Plant Protection, Russian Academy of Agricultural Sciences, Pushkin, 196608 Saint Petersburg, Russia
Victor Kuznetsov
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
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.
