Novel thiazonaphthalimides as efficient antitumor and DNA photocleaving agents: effects of intercalation, side chains, and substituent groups

Bioorg Med Chem. 2005 Aug 15;13(16):4864-70. doi: 10.1016/j.bmc.2005.05.006.

Abstract

A series of novel antitumor and DNA photocleaving agents was designed and synthesized by fusing a (substituted) thiazole ring to the naphthalimide skeletons. C1, the most active compound against A549, was about 30-fold more cytotoxic than the compound amonafide. A1, the most active compound against P388, was about 6-fold more cytotoxic than amonafide. C2, the most efficient DNA intercalator, showed the strongest DNA photocleaving activity via superoxide anion produced under UV light at 360 nm.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine
  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cattle
  • Cell Line, Tumor
  • DNA / chemistry
  • DNA / drug effects*
  • DNA / metabolism
  • DNA / radiation effects*
  • DNA, Superhelical / chemistry
  • DNA, Superhelical / drug effects
  • DNA, Superhelical / metabolism
  • DNA, Superhelical / radiation effects
  • Drug Screening Assays, Antitumor
  • Humans
  • Imides / chemistry
  • Imides / pharmacology
  • Intercalating Agents / chemical synthesis
  • Intercalating Agents / chemistry
  • Intercalating Agents / pharmacology
  • Isoquinolines / chemistry
  • Isoquinolines / pharmacology
  • Leukemia P388 / drug therapy
  • Lung Neoplasms / drug therapy
  • Magnetic Resonance Spectroscopy
  • Mice
  • Models, Molecular
  • Naphthalenes / chemical synthesis
  • Naphthalenes / chemistry*
  • Naphthalenes / pharmacology*
  • Naphthalimides
  • Organophosphonates
  • Phthalimides / chemical synthesis
  • Phthalimides / chemistry*
  • Phthalimides / pharmacology*
  • Structure-Activity Relationship
  • Thiadiazines / chemical synthesis
  • Thiadiazines / chemistry
  • Thiadiazines / pharmacology
  • Ultraviolet Rays

Substances

  • Antineoplastic Agents
  • DNA, Superhelical
  • Imides
  • Intercalating Agents
  • Isoquinolines
  • Naphthalenes
  • Naphthalimides
  • Organophosphonates
  • Phthalimides
  • Thiadiazines
  • amonafide
  • naphthalene
  • DNA
  • calf thymus DNA
  • Adenine