A comparative ADME study of aminopterin derivatives and methotrexate as anti cancer drug

In designing new drugs, drug development includes the evaluation of efficacy and toxicity of the new drug candidates. Thus, precise data on the pharmacokinetics and metabolism must be available to determine the final success or failure of the compound. Screening absorption, distribution, metabolism and excretion (ADME) is necessary to decrease the cost and the ratio of failed compounds in clinical trials 1. Methotrexate is an inhibitor of dihydrofolate reductase (DHFR), as a target for anticancer drugs 2, 3. It acts by blocking the body’s use of folic acid. As methotrexate can decrease the levels of folate, this leads folate deficiency 4 and additionally it concludes some other side effects such as liver damage which may lead to fibrosis or cirrhosis and severe skin rashes 5. Thus, scientists try to find newer and safer replacements 6. The present study incorporates ADME results of methotrexate and aminopterin derivatives as a less toxic replacement for methotrexate. All data were collected by swiss ADME prediction 7. Herein the results of lipophilicity determination of aminopterin and some derivatives are investigated.

Keywords:

aminopterin , methotrexate , ADME properties , in silico