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Synthesis and evaluation of aporphinoid 5-HTR ligands as inhibitors of PC3 prostate cancer cell growth.

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Bioorganic & medicinal chemistry letters 📖 저널 OA 8.1% 2022: 0/1 OA 2023: 0/1 OA 2024: 0/2 OA 2025: 2/22 OA 2026: 3/36 OA 2022~2026 2025 Vol.128() p. 130328
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Okpattah D, Karki A, Pillarsetty NVK, Harding WW

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Aporphines are a class of isoquinoline alkaloids that are endowed with a range of biological activities.

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APA Okpattah D, Karki A, et al. (2025). Synthesis and evaluation of aporphinoid 5-HTR ligands as inhibitors of PC3 prostate cancer cell growth.. Bioorganic & medicinal chemistry letters, 128, 130328. https://doi.org/10.1016/j.bmcl.2025.130328
MLA Okpattah D, et al.. "Synthesis and evaluation of aporphinoid 5-HTR ligands as inhibitors of PC3 prostate cancer cell growth.." Bioorganic & medicinal chemistry letters, vol. 128, 2025, pp. 130328.
PMID 40633811 ↗

Abstract

Aporphines are a class of isoquinoline alkaloids that are endowed with a range of biological activities. The 5-HT7R is an emerging biological target for prostate cancer therapeutics. In this manuscript, we report the synthesis and evaluation of aporphine enantiomers as 5-HT7R ligands, as well as their activity in inhibiting the proliferation of prostate cancer cells (specifically, PC3). The (S)-enantiomers displayed higher affinity at the 5-HT7R than the racemates and the (R)-enantiomer counterparts. The (S)-enantiomers were found to be antagonists at the 5-HT7R. Racemates as well as their respective enantiomers were selective for the 5-HT7R receptor over other serotonin and dopamine receptors evaluated. In the anticancer activity assays, the compounds showed more potent cytotoxic effects than the selective 5-HT7R antagonist control SB269970. However, no correlation was observed between the 5-HT7R affinity or 5-HT7R antagonist activity and anticancer potency, suggesting that other non-5-HT7R mechanisms play a role in the anticancer effects of the compounds. Compounds (R)-1 and (R)-4 were identified as the most potent anti-proliferative compounds and will be useful as lead molecules for prostate cancer therapeutic development in future studies.

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