Droserone and dioncoquinone B, and related naphthoquinones as potent antiausterity agents against human PANC-1 pancreatic cancer cells

Maneenet, Juthamart; Tajuddeen, Nasir; Hong Nguyen, Hung; Fujii, Rintaro; Kimbadi Lombe, Blaise; Feineis, Doris; Awale, Suresh; Bringmann, Gerhard

doi:10.1016/j.rechem.2024.101352

Cited by 3 publications

References 52 publications

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In Vitro and In Vivo Biological Evaluation of Novel 1,4‐Naphthoquinone Derivatives as Potential Anticancer Agents

Ravichandiran,

Martyna,

Kochanowicz

et al. 2024

ChemMedChem

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A novel library of naphthoquinone derivatives (3–5aa) was synthesized and evaluated for their anticancer properties. Specifically, compounds 5i, 5l, 5o, 5q, 5r, 5s, 5t, and 5v demonstrated superior cytotoxic activity against the cancer cell lines that were studied. Notably, compound 5v displayed a greater cytotoxic effect on MCF‐7 cells compared to the standard drug doxorubicin. To further investigate the mechanism of cytotoxic effect, additional anticancer studies were conducted with 5v in MCF‐7 cells. The findings showed that 5v triggered cytotoxic effects in MCF‐7 cells through the initiation of cell cycle arrest at the G1/S phase and necrosis. In vivo ecotoxicity studies indicated that 5v had lower toxicity towards zebrafish larvae (LC50 = 50.15 μM) and had an insignificant impact on cardiac functions. In vivo xenotransplantation of MCF‐7 cells in zebrafish larvae demonstrated a significant reduction in tumour volume in the xenograft. Approximately 95% of the zebrafish larvae with 5v xenografts survived after 10 days of the treatment. Finally, a computational modelling study was conducted on four protein receptors, namely ER, EFGR, BRCA1, and VEFGR2. The findings highlight the importance of the aminonaphthoquinone moiety, amide linkage, and propyl thio moiety in enhancing the anticancer properties.

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In Vitro and In Vivo Biological Evaluation of Novel 1,4‐Naphthoquinone Derivatives as Potential Anticancer Agents

Ravichandiran,

Martyna,

Kochanowicz

et al. 2024

ChemMedChem

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Structural variety and pharmacological potential of naphthylisoquinoline alkaloids

Feineis,

Bringmann

2024

The Alkaloids: Chemistry and Biology

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Targeting Pancreatic Cancer with Novel Nicolaioidesin C Derivatives: Molecular Mechanism, In Vitro, and In Vivo Evaluations

Yamazaki,

Phan,

Maneenet

et al. 2024

J. Med. Chem.

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Pancreatic cancer, one of the deadliest cancers with the lowest 5-year survival rate, often develops resistance to gemcitabine-based chemotherapies. The hypovascular nature of pancreatic tumors forces cancer cells to adapt to nutrient-depleted tumor microenvironments. Conventional anticancer agents targeting rapidly dividing cancer cells under nutrient-rich conditions are largely ineffective against adapted pancreatic cancer cells. Thus, targeting cancer cells under nutrient starvation, termed the “antiausterity strategy”, may be effective for pancreatic cancer. This study examined nicolaioidesin C (Nic-C) derivatives as antiausterity agents. Among the 32 derivatives, Nic-15 (4n) exhibited superior cytotoxicity against MIA PaCa-2 and PANC-1 pancreatic cancer cells, inhibited MIA PaCa-2 cell migration and colony formation, and modulated the PI3K/Akt/mTOR pathway, while reducing the ER stress markers induced by gemcitabine. Nic-15 was found to inhibit tumor growth and enhance the efficacy of gemcitabine in an in vivo xenograft model. Nic-15 in combination with gemcitabine may be an effective strategy for the treatment of pancreatic cancer.

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Droserone and dioncoquinone B, and related naphthoquinones as potent antiausterity agents against human PANC-1 pancreatic cancer cells

Cited by 3 publications

References 52 publications

In Vitro and In Vivo Biological Evaluation of Novel 1,4‐Naphthoquinone Derivatives as Potential Anticancer Agents

In Vitro and In Vivo Biological Evaluation of Novel 1,4‐Naphthoquinone Derivatives as Potential Anticancer Agents

Structural variety and pharmacological potential of naphthylisoquinoline alkaloids

Targeting Pancreatic Cancer with Novel Nicolaioidesin C Derivatives: Molecular Mechanism, In Vitro, and In Vivo Evaluations

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