2. Academic Validation
  3. Towards lead compounds as anti-cancer agents via new phaeosphaeride A derivatives

Towards lead compounds as anti-cancer agents via new phaeosphaeride A derivatives

  • Bioorg Med Chem Lett. 2019 Jan 1;29(1):59-61. doi: 10.1016/j.bmcl.2018.11.003.
Victoria V Abzianidze 1,  Sofya A Zakharenkova 2,  Natalia I Moiseeva 3,  Petr P Beltyukov 4,  Valeriy A Polukeev 5,  Yaroslav A Dubrovskii 6,  Victor A Kuznetsov 4,  Yuri G Trishin 2,  Jennifer E Mejia 7,  Alvin A Holder 8
Affiliations

Affiliations

  • 1 Research Institute of Hygiene, Occupational Pathology and Human Ecology, Federal Medical Biological Agency, p/o Kuz'molovsky, Saint Petersburg 188663, Russian Federation. Electronic address: vvaavv@mail.ru.
  • 2 Saint Petersburg State University of Industrial Technologies and Design, Saint Petersburg 198095, Russian Federation.
  • 3 N.N. Blokchin National Medical Research Center of Oncology, Moscow 115478, Russian Federation.
  • 4 Research Institute of Hygiene, Occupational Pathology and Human Ecology, Federal Medical Biological Agency, p/o Kuz'molovsky, Saint Petersburg 188663, Russian Federation.
  • 5 Institute of Experimental Medicine, Saint Petersburg 197376, Russian Federation.
  • 6 Research Institute of Hygiene, Occupational Pathology and Human Ecology, Federal Medical Biological Agency, p/o Kuz'molovsky, Saint Petersburg 188663, Russian Federation; Saint Petersburg State University, Institute of Chemistry, Saint Petersburg 198504, Russian Federation.
  • 7 Department of Chemistry and Biochemistry, Old Dominion University, 4541 Hampton Boulevard, Norfolk, VA 23529, United States.
  • 8 Department of Chemistry and Biochemistry, Old Dominion University, 4541 Hampton Boulevard, Norfolk, VA 23529, United States. Electronic address: aholder@odu.edu.
PMID: 30447888 DOI: 10.1016/j.bmcl.2018.11.003
Abstract

New derivatives of phaeosphaeride A (PPA) were synthesized and characterized. Anti-tumor studies were carried out on the U937, HCT-116, PC3, MCF-7, A549, К562, NCI-H929, Jurkat, THP-1, RPMI8228 tumor cell lines, and on the HEF cell line. All the compounds synthesized were found to have better efficacy than PPA towards the tumor cell lines mentioned. Compound 6 (IC50 = 0.59 ± 0.27 µM) was observed to be 11 times more active than PPA (IC50 = 6.5 ± 0.30 µM) towards the NCI-H929 cell line, with a therapeutic index of 18. Compound 6 was determined to be over half and 16 times more active than etoposide towards the NCI-H929 (IC50 = 0.9 ± 0.05 µM) and A549 (IC50 = 100 ± 7.0 µM) cell lines, respectively.

Keywords

Anti-cancer agents; Etoposide; HCT-116 cell line; HEF cell line; In vitro studies; Mercapto derivative; Natural products; Phaeosphaeride A; Therapeutic index.

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