Synthesis, in vitro structure-activity relationship, and in vivo studies of 2-arylthiazolidine-4-carboxylic acid amides as anticancer agents

Yan Lu, Zhao Wang, Chien Ming Li, Jianjun Chen, James T. Dalton, Wei Li, Duane Miller

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

A series of (2RS,4R)-2-arylthiazolidine-4-carboxylic acid amide (ATCAA) was synthesized. Antiproliferative activity against melanoma and prostate cancer cells compared with control cells (fibroblast and RH7777, respectively) was evaluated. Compound 3id showed the best selectivity and growth-inhibition activity against three melanoma cell lines (B16-F1, A375, and WM-164). Compounds 15b and 3ac had good selectivity and potency against four prostate cancer cell lines (DU 145, PC-3, LNCaP, and PPC-1). The structure-activity relationship (SAR) of the side chain, the thiazolidine ring, and phenyl substituents is discussed. Cell cycle analysis showed that the percentage of cancer cells undergoing apoptosis (sub-G1 phase) increased after treatment with 1b and 3ad, which also strongly inhibited melanoma colony formation. In vivo studies on nude mice bearing A375 melanoma tumors showed that compound 1b inhibited tumor growth in a dose-dependent manner. At a dose of 10 mg/kg, 1b significantly inhibited melanoma tumor growth and showed higher efficacy than did dacarbazine at 60 mg/kg.

Original languageEnglish (US)
Pages (from-to)477-495
Number of pages19
JournalBioorganic and Medicinal Chemistry
Volume18
Issue number2
DOIs
StatePublished - Jan 15 2010

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Structure-Activity Relationship
Carboxylic Acids
Amides
Antineoplastic Agents
Melanoma
Cells
Tumors
Neoplasms
Prostatic Neoplasms
Bearings (structural)
Growth
Thiazolidines
Cell Line
Dacarbazine
G1 Phase
Fibroblasts
Nude Mice
Cell Cycle
In Vitro Techniques
Apoptosis

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Synthesis, in vitro structure-activity relationship, and in vivo studies of 2-arylthiazolidine-4-carboxylic acid amides as anticancer agents. / Lu, Yan; Wang, Zhao; Li, Chien Ming; Chen, Jianjun; Dalton, James T.; Li, Wei; Miller, Duane.

In: Bioorganic and Medicinal Chemistry, Vol. 18, No. 2, 15.01.2010, p. 477-495.

Research output: Contribution to journalArticle

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