In vivo antitumor, in vitro antibacterial activity and alkylating properties of phosphorohydrazine derivatives of coumarin and chromone

Eur J Med Chem. 2006 Nov;41(11):1301-9. doi: 10.1016/j.ejmech.2006.06.004. Epub 2006 Aug 14.

Abstract

The aim of this research was to examine chemical and biological properties of the products (4a-c/5a-c, 8b-c, 9a-b) of the reaction of methyl chromone-3-carboxylate (2), 3-formyl-4-hydroxycoumarin (3), 3-formylchromone (6) and chromone 3-carbonyl chloride (7) with phosphorus hydrazides (1a-c). For structure and keto-enol tautomerism analyses (1)H, (13)C, (31)P NMR spectroscopy was used. The ring transformation species (4a-c/5a-c) containing the coumarin ring (5a-c) were predominant in the solution. The chromone series 8b-c and 9a-b was obtained in reaction of phosphorus hydrazides (1a-c) with 3-formylchromone (6) and chromone-3-carbonyl chloride (7). Alkylating activity of phosphorohydrazides of coumarin and chromone was determined with in vitro Preussmann test (NBP test). Some of the compounds were examined towards antitumor and antibacterial activity. Compounds 4b-c/5b-c and 9a demonstrated in vitro antitumor activity against P388 leukemia. Antineoplastic activity of the compounds 4b/5b and 9a combined with methotrexate was showed using L1210 murine leukemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Antineoplastic Agents, Alkylating / chemical synthesis*
  • Antineoplastic Agents, Alkylating / chemistry
  • Antineoplastic Agents, Alkylating / pharmacology
  • Chromones / chemical synthesis
  • Chromones / chemistry
  • Chromones / pharmacology*
  • Coumarins / chemical synthesis
  • Coumarins / chemistry
  • Coumarins / pharmacology*
  • Gram-Negative Bacteria / drug effects
  • Gram-Positive Bacteria / drug effects
  • Hydrazones / chemical synthesis
  • Hydrazones / chemistry
  • Hydrazones / pharmacology*
  • Leukemia L1210 / drug therapy
  • Leukemia P388 / drug therapy
  • Magnetic Resonance Spectroscopy
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred DBA
  • Microbial Sensitivity Tests

Substances

  • Anti-Bacterial Agents
  • Antineoplastic Agents, Alkylating
  • Chromones
  • Coumarins
  • Hydrazones