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Marine-derived bisindoles exhibit structural diversity and exert anti-cancer influence through multiple mechanisms. Comprehensive research has shown that the development success rate of drugs derived from marine natural products is four times higher than that of other natural derivatives. Currently, there are 20 marine-derived drugs used in clinical practice, with 11 of them demonstrating anti-tumor effects. This article provides a thorough review of recent advancements in anti-tumor exploration involving 167 natural marine bisindole products and their derivatives. Not only has enzastaurin entered clinical practice, but there is also a successfully marketed marine-derived bisindole compound called midostaurin that is used for the treatment of acute myeloid leukemia. In summary, investigations into the biological activity and clinical progress of marine-derived bisindoles have revealed their remarkable selectivity, minimal toxicity, and efficacy against various cancer cells. Consequently, they exhibit immense potential in the field of anti-tumor drug development, especially in the field of anti-tumor drug resistance. In the future, these compounds may serve as promising leads in the discovery and development of novel cancer therapeutics. [ABSTRACT FROM AUTHOR]

Benzophenanthridine alkaloids are a class of isoquinoline compounds, which are widely found in the plants of papaveraceae, corydalis, and rutaceae. Biological activities and clinical studies have shown that benzophenanthridine alkaloids have inhibitory effects on many cancers. Considering that the anticancer activities and mechanisms of many natural benzophenanthridine alkaloids have been discovered in succession, the purpose of this paper is to review the anticancer effects of benzophenanthridine alkaloids and explore the application potential of these natural products in the development of antitumor drugs. A literature survey was carried out using Scopus, Pubmed, Reaxys, and Google Scholar databases. This review summarizes and analyzes the current status of research on the antitumor activity and antitumor mechanism of natural products of benzophenanthridine from different sources. The research progress of the antitumor activity of natural products of benzophenanthridine from 1983 to 2023 was reviewed. The antitumor activities of 90 natural products of benzophenanthridine and their related analogues were summarized, and the results directly or indirectly showed that natural products of benzophenanthridine had the effects of antidrug-resistant tumor cell lines, antitumor stem cells, and inducing ferroptosis. In conclusion, benzophenanthridine alkaloids have inhibitory effects on a variety of cancers and have the potential to counteract tumor resistance, and they have great application potential in the development of antitumor drugs. [ABSTRACT FROM AUTHOR]

There iridium(III) complexes, [Ir(3-MeO-Phtpy)Cl 3 ] ( 1 ), [Ir(2-MeO-Phtpy)Cl 3 ] ( 2 ) and [Ir(4-MeO-Phtpy)Cl 3 ] ( 3 ) with 4′-(3-methoxyphenyl)-2,2′:6′,2″-terpyridine (3-MeO-Phtpy), 4′-(2-methoxyphenyl)-2,2′:6′,2″-terpyridine (2-MeO-Phtpy) and 4′-(4-methoxyphenyl)-2,2′:6′,2″-terpyridine (4-MeO-Phtpy) as ligands, respectively, were synthesized and evaluated for their antiproliferative activities. In these complexes, the iridium(III) center adopts a six-coordinate distorted octahedral geometry. Among them, complex 1 exhibited the most potent activity, with IC 50 values of 3.19–27.77 μ M against four cancer cell lines (BEL-7404, Hep-G2, NCI-H460 and MGC80-3 cells). Cellular mechanism studies suggested that complexes 1 – 3 directly targeted c-myc promoter elements and inhibited the telomerase activity. In addition, complexes 1 – 3 may trigger cell apoptosis via a mitochondrial dysfunction pathway. We postulated that the difference in the in vitro antitumor activities of complexes 1 – 3 is mainly dependent on the position of the methoxy group on the phenyl ring of the iridium ligand. [ABSTRACT FROM AUTHOR]

A series of hybrids of scopoletin and substituted cinnamic acid were designed, synthesized and evaluated in vitro and in vivo against five human tumor cell lines [MCF-7, MDA-MB-231, A549, HCT-116, and HeLa] with doxorubicin as the positive control. Compounds 17a , 17b , 17c and 17g exhibited potent cytotoxic activity. Especially, compound 17b displayed broad spectrum activity with IC 50 values ranging from 0.249 μM to 0.684 μM. Moreover, in a preliminary pharmacological study, 17b not only remarkably induced cellular apoptosis, but also clearly induced A549 cells cycle arrest at S phase. In vivo study showed that 17b significantly suppressed tumor growth in a dose-dependent manner without causing the loss of the mean body weight of mice, which was superior to doxorubicin. These preliminary results indicate that 17b is an optimal anti-cancer leading compound and merit further structural modification. [ABSTRACT FROM AUTHOR]

Highlights: [•] A new dual-function peptide was isolated from the venom of Buthus martensii Karsch and was designated BmK AGAP-SYPU2. [•] Its primary sequence was deduced from the results of Edman degradation, trypsin fragmentation, MALDI-TOF-MS and cDNA cloning. [•] Pharmacological analysis revealed that BmK AGAP-SYPU2 had dual-functions of antitumor and analgesic activities in whole-animal tests. [•] Sequence alignment and homology modeling showed that BmK AGAP-SYPU2 is highly conserved relative to other scorpion α-toxins. [Copyright &y& Elsevier]

Abstract: Using structure-based drug design, we identified and optimized a novel series of pyrimidodiazepinone PLK1 inhibitors resulting in the selection of the development candidate TAK-960. TAK-960 is currently undergoing Phase I evaluation in adult patients with advanced solid malignancies. [Copyright &y& Elsevier]

Highlights: [•] The potent anti-tumor components in Z. ailanthoides were investigated. [•] The silica gel chromatography and HPCCC were used successively. [•] Luvangetin, xanthyletin, hinokinin and asarinin were isolated and identified. [•] Asarinin was firstly isolated from this plant to the best of our knowledge. [Copyright &y& Elsevier]