Tylophorine

Tylophorine is an alkaloid first isolated in 1935 from plants of the genus Tylophora. Studies have demonstrated that this class of alkaloids, characterized by a phenanthroindolizidine skeleton, exhibits potent antitumor, anti-inflammatory, and antiviral activities. A representative tylophorine analogue, DCB-3503 (NSC-716802, 1), displayed an average GI₅₀ value of approximately 10⁻⁸ M against 59 human tumor cell lines in the National Cancer Institute (NCI) anticancer drug screening panel and also inhibited the proliferation of multidrug-resistant tumor cells. Tylocrebrine, another representative member of this class, advanced to Phase I clinical trials as a potential antitumor agent but was subsequently withdrawn because of severe neurotoxicity. Although extensive studies have investigated the antitumor mechanisms of tylophorine alkaloids, their direct molecular targets remain unclear.[1]

(+)-(S)-Tylophorine is a a major alkaloid of Tylophora indica. (+)-(S)-Tylophorine is an immunosuppressant and inflammation inhibitor. (+)-(S)-Tylophorine showed antiproliferative activity and induction of apoptosis in tumor cells.

ChEBI: Tylophorine is an organonitrogen heterocyclic compound and an organic heteropentacyclic compound.

[1] Liu, Yuxiu, et al. “6-OH-Phenanthroquinolizidine Alkaloid and Its Derivatives Exert Potent Anticancer Activity by Delaying S Phase Progression.” Journal of Medicinal Chemistry, 60 7, 2017, pp. 2764–79, https://doi.org/10.1021/acs.jmedchem.6b01502.
[2] Zeng, W., and S. Chemler. “Synthesis of (S)-(+)-Tylophorine.” Synfacts, 22 1, 2009, pp. 0004–0004, https://doi.org/10.1055/s-0028-1087241.
[3] Masal, Dattatraya P., and D. Srinivasa Reddy. “Gram-Scale Synthesis of (±)-Tylophorine.” Synlett, 55 1, 2024, https://doi.org/10.1055/a-2351-4828.
[4] Sotto, Antonella Di, et al. “Benzoindolizidine Alkaloids Tylophorine and Lycorine and Their Analogues with Antiviral, Anti-Inflammatory, and Anticancer Properties: Promises and Challenges.” Biomedicines, 11 10, 2023, https://doi.org/10.3390/biomedicines11102619.