Basic Information
ID: ALA4610125
Journal: J Med Chem
Title: Evaluation of Manassantin A Tetrahydrofuran Core Region Analogues and Cooperative Therapeutic Effects with EGFR Inhibition.
Authors: Kwak SH, Stephenson TN, Lee HE, Ge Y, Lee H, Min SM, Kim JH, Kwon DY, Lee YM, Hong J.
Abstract: Tumors adapt to hypoxia by regulating angiogenesis, metastatic potential, and metabolism. These adaptations mediated by hypoxia-inducible factor 1 (HIF-1) make tumors more aggressive and resistant to chemotherapy and radiation. Therefore, HIF-1 is a validated therapeutic target for cancer. In order to develop new HIF-1 inhibitors for cancer chemotherapy by harnessing the potential of the natural product manassantin A, we synthesized and evaluated manassantin A analogues with modifications in the tetrahydrofuran core region of manassantin A. Our structure-activity relationship study indicated that the α,α'-trans-configuration of the central ring of manassantin A is critical to HIF-1 inhibition. We also demonstrated that a combination of manassantin A with an epidermal growth factor receptor inhibitor shows cooperative antitumor activity (∼80% inhibition for combination vs ∼30% inhibition for monotherapy). Our findings will provide important frameworks for the future therapeutic development of manassantin A-derived chemotherapeutic agents.
CiteXplore: 32579356
DOI: 10.1021/acs.jmedchem.0c00151
Patent ID: ┄
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