Synthesis, Computational Docking Study, and Biological Evaluation of a Library of Heterocyclic Curcuminoids with Remarkable Antitumor Activity

Kenneth K. Laali, William J. Greves, Angela T. Zwarycz, Sebastian J. Correa Smits, Frederick J. Troendle, Gabriela L. Borosky, Sharoon Akhtar, Alak Manna, Aneel Paulus, Asher A Chanan Khan, Manabu Nukaya, Gregory D. Kennedy

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

In a continuing search for curcuminoid (CUR) compounds with antitumor activity, a novel series of heterocyclic CUR–BF2 adducts and CUR compounds based on indole, benzothiophene, and benzofuran along with their aryl pyrazoles were synthesized. Computational docking studies were performed to compare binding efficiency to target proteins involved in specific cancers, namely HER2, proteasome, VEGFR, BRAF, and Bcl-2, versus known inhibitor drugs. The majority presented very good binding affinities, similar to, and even more favorable than those of known inhibitors. The indole-based CUR–BF2 and CUR compounds and their bis-thiocyanato derivatives exhibited high anti-proliferative and apoptotic activity by in vitro bioassays against a panel of 60 cancer cell lines, more specifically against multiple myeloma (MM) cell lines (KMS11, MM1.S, and RPMI-8226) with significantly lower IC50 values versus healthy PBMC cells; they also exhibited higher anti-proliferative activity in human colorectal cancer cells (HCT116, HT29, DLD-1, RKO, SW837, and Caco2) than the parent curcumin, while showing notably lower cytotoxicity in normal colon cells (CCD112CoN and CCD841CoN).

Original languageEnglish (US)
Pages (from-to)1895-1908
Number of pages14
JournalChemMedChem
Volume13
Issue number18
DOIs
StatePublished - Sep 19 2018

Fingerprint

Libraries
Cells
Pyrazoles
HCT116 Cells
Cell Line
HT29 Cells
Curcumin
Proteasome Endopeptidase Complex
Multiple Myeloma
Human Activities
Biological Assay
Inhibitory Concentration 50
Colorectal Neoplasms
Neoplasms
Colon
Bioassay
Cytotoxicity
Pharmaceutical Preparations
Derivatives
Proteins

Keywords

  • antitumor agents
  • apoptosis
  • binding affinity
  • curcuminoids
  • multiple myeloma

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

Cite this

Laali, K. K., Greves, W. J., Zwarycz, A. T., Correa Smits, S. J., Troendle, F. J., Borosky, G. L., ... Kennedy, G. D. (2018). Synthesis, Computational Docking Study, and Biological Evaluation of a Library of Heterocyclic Curcuminoids with Remarkable Antitumor Activity. ChemMedChem, 13(18), 1895-1908. https://doi.org/10.1002/cmdc.201800320

Synthesis, Computational Docking Study, and Biological Evaluation of a Library of Heterocyclic Curcuminoids with Remarkable Antitumor Activity. / Laali, Kenneth K.; Greves, William J.; Zwarycz, Angela T.; Correa Smits, Sebastian J.; Troendle, Frederick J.; Borosky, Gabriela L.; Akhtar, Sharoon; Manna, Alak; Paulus, Aneel; Chanan Khan, Asher A; Nukaya, Manabu; Kennedy, Gregory D.

In: ChemMedChem, Vol. 13, No. 18, 19.09.2018, p. 1895-1908.

Research output: Contribution to journalArticle

Laali, KK, Greves, WJ, Zwarycz, AT, Correa Smits, SJ, Troendle, FJ, Borosky, GL, Akhtar, S, Manna, A, Paulus, A, Chanan Khan, AA, Nukaya, M & Kennedy, GD 2018, 'Synthesis, Computational Docking Study, and Biological Evaluation of a Library of Heterocyclic Curcuminoids with Remarkable Antitumor Activity', ChemMedChem, vol. 13, no. 18, pp. 1895-1908. https://doi.org/10.1002/cmdc.201800320
Laali, Kenneth K. ; Greves, William J. ; Zwarycz, Angela T. ; Correa Smits, Sebastian J. ; Troendle, Frederick J. ; Borosky, Gabriela L. ; Akhtar, Sharoon ; Manna, Alak ; Paulus, Aneel ; Chanan Khan, Asher A ; Nukaya, Manabu ; Kennedy, Gregory D. / Synthesis, Computational Docking Study, and Biological Evaluation of a Library of Heterocyclic Curcuminoids with Remarkable Antitumor Activity. In: ChemMedChem. 2018 ; Vol. 13, No. 18. pp. 1895-1908.
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