- Scaffold Hopping of Natural Product Evodiamine: Discovery of a Novel Antitumor Scaffold with Excellent Potency against Colon Cancer
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Inspired by the natural product evodiamine, a novel antitumor indolopyrazinoquinazolinone scaffold was designed by scaffold hopping. Structure-activity relationship studies led to the discovery of compound 15j, which shows low nanomolar inhibitory activity against the HCT116 cell line. Further antitumor mechanism studies indicated that compound 15j acted by the dual inhibition of topoisomerase 1 and tubulin and induced apoptosis with G2 cell-cycle arrest. The quaternary ammonium salt of compound 15j (compound 15js) exhibited excellent in vivo antitumor activity (TGI = 66.6%) in the HCT116 xenograft model with low toxicity. Indolopyrazinoquinazolinone derivatives represent promising multitargeting antitumor leads for the development of novel antitumor agents.
- Wang, Lei,Fang, Kun,Cheng, Junfei,Li, Yu,Huang, Yahui,Chen, Shuqiang,Dong, Guoqiang,Wu, Shanchao,Sheng, Chunquan
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p. 696 - 713
(2020/02/04)
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- SMALL MOLECULES FOR INHIBITING MALE FERTILITY
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Compounds suitable for use in providing male contraception, an assay method for identifying such compounds, and methods of providing contraception using the compounds, are provided. In one embodiment, the compounds described herein mimic the binding of anti-EPPIN antibodies to EPPIN, and thus inhibit the forward motility of sperm in humans and other primates. In another embodiment, the compounds described herein inhibit or enhance EPPIN-semenogelin binding, and inhibit forward motility of sperm. The assays described herein identify compounds which inhibit sperm motility, and can be carried out in a high throughput manner, using labeled recombinant EPPIN and semenogelin. The compounds can be used in oral or transdermal compositions to temporarily and reversibly inhibit male fertility. They can also be used in addition to, or in place of, spermicides in spermicidal compositions, such as those used in conjunction with condoms, diaphragms, and spermicidal jellies.
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Page/Page column 50; 53
(2015/10/05)
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- 2,4-Bis(octadecanoylamino)benzenesulfonic acid sodium salt as a novel scavenger receptor inhibitor with low molecular weight
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In order to investigate the effect of the fixation of the orientations of the two long chains, three types of novel derivatives of scavenger receptor inhibitor 1 were synthesized, and their biological activities were evaluated. Among the novel derivatives
- Yoshiizumi, Kazuya,Nakajima, Fumio,Dobashi, Rika,Nishimura, Noriyasu,Ikeda, Shoji
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p. 2791 - 2795
(2007/10/03)
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- REACTIONS OF 2-METHYLPYRAZOLOQUINAZOLIN-9-ONE DERIVATIVES
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The directions of reactions of the titlie compounds (1) with formaldehyde and amines (secondary and primary) and with aromatic aldehydes, have been studied.It has been found that hydrogen atom substitution in position 3 is favorized.As a result of peracet
- Hahn, Witold E.,Osinski, Janusz
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p. 411 - 424
(2007/10/02)
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