Integrated scientific data bases review on asulacrine and associated toxicity.
Asulacrine (ASL), a weakly basic and highly lipophilic drug was synthesized in 1980's in cancer research laboratory of Auckland by modifications to the acridine portion of amsacrine on 3-, 4- and 5-substitution patterns. In contrast to its precursor amsacrine (m-AMSA), ASL was effective not only against leukemia and Lewis lung tumor system but also a wide variety of solid tumor. Its metabolic pathway is not same to amsacrine hence different side effects, hepatotoxicity and excretion was observed. Asulacrine is under phase II clinical trials and has showed promising results but its toxicity especially phlebitis is stumbling block in its clinical implementation. This review is an effort to give a possible clue, based on scientifically proven results, to the researchers to solve the mystery of associated toxicity, phlebitis. Review covers the available literature on asulacrine and other acridine derivatives regarding pharmacology, pharmacokinetics, quantitative structure activity relationship and toxicology via electronic search using scientific databases like PubMed and others. To date, all abstracts and full-text articles were discussed and analyzed. The tabulated comparisons and circuitry mechanism of ASL are the added features of the review which give a complete understanding of hidden aspects of possible route cause of associated toxicity, the phlebitis.
Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University (CPU), Nanjing, China. Electronic address: attiapharm@gmail.com.
Attia
A
Afzal
School of Pharmacy, Tongji Medical College of Huazhong University of Science and Technology (HUST), Wuhan, China. Electronic address: chiefpharm@gmail.com.
Muhammad
M
Sarfraz
School of Pharmacy, University of Auckland, New Zealand. Electronic address: z.wu@auckland.ac.nz.
Zimei
Z
Wu
Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University (CPU), Nanjing, China. Electronic address: guangjiwang@hotmail.com.
Guangji
G
Wang
Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University (CPU), Nanjing, China. Electronic address: jgsun@cpu.edu.cn.
Jianguo
J
Sun
D000677:Amsacrine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D018384:Oxidative Stress / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D000677:Amsacrine; C042315:asulacrine
Amsacrine; Anilinoacridine derivatives; Asulacrine; DACA; Phlebitis; Structure activity relationship (SAR)