Abstract
Derivatives of the new ring systems bispyrido[4',3':4,5]pyrrolo[1,2-a:1',2'-d]pyrazine-6,13-dione and its deaza analogue pyrido[4'',3'':4',5']pyrrolo-[1',2':4,5]pyrazino[1,2-a]indole-6,13-dione were conveniently synthesized through a four-step sequence. Symmetrical derivatives of the former ring system were obtained through self condensation. On the other hand, condensation of 6-azaindole carboxylic acid with indole 2-carboxylic acid afforded the deaza analogue ring system. Derivatives of the title ring system were tested by the National Cancer Institute (Bethesda, MD, USA) and four of them exhibited modest activity against MCF7 (a breast cancer cell line) and/or UO-31 (a renal cancer cell line).
Highlights
Piperazine-2,5-diones represent a very interesting class of compounds because this heterocyclic system is found in many unique natural products [1]
All derivatives were prescreened according to the NCI protocol at 10−5 M dose on the full panel of 60 human cancer cell lines derived from nine human cancer cell types that have been grouped in disease sub-panels including leukemia, non-small-cell lung, colon, central nervous system, melanoma, ovarian, renal, prostate and breast tumour cell lines.[32]
We have reported the synthesis of derivatives of the new ring systems
Summary
Piperazine-2,5-diones represent a very interesting class of compounds because this heterocyclic system is found in many unique natural products [1]. In recent years there has been a growing awareness of the diversity and biological roles played by many diketopiperazines among the over one-hundred found in Nature. Molecules 2014, 19 compounds show antineoplastic activity, in particular phenylahistin (1, Figure 1), a fungal metabolite isolated from culture broths of Aspergillus ustus NFC-F038, which is a result of a condensation between L-phenylalanine and an isoprenylated dehydrohistidine residue with a quaternary carbon at C-5 of the imidazole ring [2]. Phenylahistin derivatives were synthesized [5] with the aim of finding new antineoplastic derivatives, and to understand the structural features necessary for the anti-microtubule activity
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