Comparative studies between the effects of mitozolomide and two novel tetrazepinones PYRCL and QUINCL on NIH:OVCAR-3 cells

Abstract

In summary, based on (a) their effects on DNA, RNA, protein synthesis and on the cell cycle, (b) their alkylating power and (c) their interactions with DNA, the 3-(2-chloroethyl)tetrazepinones appeared to kill tumor cells by a novel mechanism which may significantly differ from that of their 3-(2-chloroethyl)-tetrazinone counterpart, mitozolomide.

Triazenes: A Versatile Tool in Organic Synthesis

“…For aryl and alkyl triazenes, proteolytic decomposition occurs under physiological conditions to give reactive alkyl diazonium compounds capable of alkylating DNA;14, 15 consequently, these compounds are carcinogenic and/or mutagenic 12. Several triazenes, however, show low animal toxicity while retaining their potency against specific tumor cell lines 16, 17…”

Furanolabdanoid–based 1,2,4‐oxadiazoles: Synthesis and cytotoxic activity

“…The latter effect is unsurprising, since the mentioned compounds with a chloromethyl substituent in the oxadiazole ring could become alkylating properties. This effect was also established for other heterocycles . So, the replacement of methyl substituent to 2‐chloroalkyl substituent in A‐ring of heterocyclic compounds such as tetrazepinones was highly detrimental for cytotoxic profile of the compounds.…”

Triazene: vielseitige Verbindungen für die organische Synthese

“…[1,2,13] Alkyl-und Arylalkyltriazene bilden unter physiologischen Bedingungen als Produkte proteolytischer Zersetzung reaktive Alkyldiazoniumionen, die DNA alkylieren kˆnnen. [16,17] 2.1. [12] Einige Triazene haben sich trotz ihrer Wirksamkeit gegen bestimmte Tumor-Zelllinien im Tierversuch als wenig toxisch erwiesen.…”

“…Die Hydrolyse von 8 f¸hrt zur Bildung eines offenkettigen Triazens, das mˆglicherweise alkylierend wirkt. [16,38,39] [16,36,37] Den Schl¸sselschritt der Synthese bildet der Ringschluss zwischen einer Diazoniumfunktion und einer Amidgruppe in ortho-Position.…”