Abstract: We have recently designed and synthesized a novel iminoquinone anticancer agent, 7-(4-fluorobenzylamino)-1,3,4,8-tetrahydropyrrolo[4,3,2-de]quinolin-8(1H)-one (FBA-TPQ) and initiated its preclinical development. Herein we investigated its efficacy, safety, and pharmacokinetics in in vitro and in vivo models of human pancreatic cancer. Our results demonstrated that FBA-TPQ inhibited pancreatic cancer cell growth, induced apoptosis, and caused cell cycle arrest in vitro. It inhibited the growth of xenograft tumors with minimal host toxicity. To facilitate future preclinical and clinical development of the agent, we also developed and validated a Rapid Resolution Liquid Chromatography (RRLC) method for quantitative analysis of FBA-TPQ in plasma and tissue samples. The method was found to be precise, accurate, and specific. Using this method, we carried out in vitro and in vivo evaluations of the pharmacological properties of FBA-TPQ, including stability in plasma, plasma protein binding, metabolism by S9 enzymes, plasma pharmacokinetics, and tissue distribution. Our results indicate that FBA-TPQ is a potential therapeutic agent for pancreatic cancer, providing a basis for future preclinical and clinical development.
This is an open access article distributed under the
Creative Commons Attribution License which permits unrestricted use, distribution,
and reproduction in any medium, provided the original work is properly cited.
Export to BibTeX
MDPI and ACS Style
Zhang, X.; Xu, H.; Zhang, X.; Voruganti, S.; Murugesan, S.; Nadkarni, D.H.; Velu, S.E.; Wang, M.-H.; Wang, W.; Zhang, R. Preclinical Evaluation of Anticancer Efficacy and Pharmacological Properties of FBA-TPQ, a Novel Synthetic Makaluvamine Analog. Mar. Drugs 2012, 10, 1138-1155.
Zhang X, Xu H, Zhang X, Voruganti S, Murugesan S, Nadkarni DH, Velu SE, Wang M-H, Wang W, Zhang R. Preclinical Evaluation of Anticancer Efficacy and Pharmacological Properties of FBA-TPQ, a Novel Synthetic Makaluvamine Analog. Marine Drugs. 2012; 10(5):1138-1155.
Zhang, Xiangrong; Xu, Hongxia; Zhang, Xu; Voruganti, Sukesh; Murugesan, Srinivasan; Nadkarni, Dwayaja H.; Velu, Sadanandan E.; Wang, Ming-Hai; Wang, Wei; Zhang, Ruiwen. 2012. "Preclinical Evaluation of Anticancer Efficacy and Pharmacological Properties of FBA-TPQ, a Novel Synthetic Makaluvamine Analog." Mar. Drugs 10, no. 5: 1138-1155.