Synthesis, analysis and biological evaluation of novel indolquinonecryptolepine analogues as potential anti-tumour agents

Abstract

A small library of cryptolepine analogues were synthesised incorporating halogens and/or nitrogen containing side chains to optimise their interaction with the sugar-phosphate backbone of DNA to give improved binding, interfering with topoisomerase II hence enhancing cytotoxicity. Cell viability, DNA binding and Topoisomerase II inhibition is discussed for these compounds. Fluorescence microscopy was used to investigate the uptake of the synthesised cryptolepines into the nucleus. We report the synthesis and anti-cancer biological evaluation of nine novel cryptolepine analogues, which have greater cytotoxicity than the parent compound and are important lead compounds in the development of novel potent and selective indoloquinone anti-neoplastic agents.

Design, Synthesis, and Antifungal Evaluation of Cryptolepine Derivatives against Phytopathogenic Fungi

“…Hence, a whole variety of bioisosterisms and salt forms of them were synthesized to explore their activities against plant pathogenic fungi. 23 From the activity data results, we found that the salt form c1 of cryptolepine exhibited an improved activity with an EC 50 of 0.041 μg/mL against B. cinerea. However, the antifungal activity of cryptolepine would become worse when the methyl at C5 was lacking.…”

“…According to the previous work reported by Ning et al, cryptolepine derivatives were prepared by replacing the nitrogen atom at position 10 with oxygen or sulfur to search for antimicrobial agents. Hence, a whole variety of bioisosterisms and salt forms of them were synthesized to explore their activities against plant pathogenic fungi . From the activity data results, we found that the salt form c1 of cryptolepine exhibited an improved activity with an EC 50 of 0.041 μg/mL against B.…”

“…The extraction and separation test revealed that it contains cryptolepine, neocryptolepine, quindoline, hydroxycryptolepine, and other ingredients. Further research revealed that the main component cryptolepine, whose total synthesis was prior to separation and determination, had exhibited unprecedented pharmacological effects, including antimalarial activity, − antibacterial activity, − anticancer activity, − antifungal activity, − anti-inflammatory activity, , antidiabetic activity, antituberculosis activity, and so on. − Although fruitful achievements had been widely reported, the exploration of cryptolepine and its derivatives in fungicide chemistry was barely conducted. This implied us that more emphasis should be laid on the study of cryptolepine and its derivatives in the control of crop fungi.…”

Base-promoted cascade β-F-elimination/electrocyclization/Diels–Alder/retro-Diels–Alder reaction: efficient access to δ-carboline derivatives

“…Carbolines, usually known as pyrido[ x , y-b ]indoles, have emerged as important N-heterocycles with a broad spectrum of biological activities, which could be divided into α-, β-, γ- and δ-carbolines according to the position of the N atom. 1,2 Among these various types of carbolines, δ-carbolines are identified as privileged units in plenty of natural alkaloids, pharmaceuticals, and functional materials (Scheme 1a). 2 For example, CzBPDCb was used as an electron transport unit bipolar host material for blue phosphorescent organic light emitting didoes, 2 a N 5 -ω-cyclohexylpentyl- N 1 -methyl-δ-carbolinium displayed antibacterial and antifungal activities, 2 b PIQ could serve as a potential structure-selective G-quadruplex binding molecule, 2 c natural alkaloid Jusbetonin was isolated from Justicia betonica , 2 d and SYUIQ-5 is a potential anticancer therapeutic.…”

Synthesis and Optical Properties of Alkaloid Quindoline, Its Structural Analogues and Substituted δ‐Carbolines

“…The search for new effective methods for the synthesis of quindoline as a cryptolepine precursor, its structural analogs and δ‐carbolines is caused by the high relevance of problems of malaria and tuberculosis control ,,…”