Novel molecular anti-colorectalcancer conjugate:chlorambucil-adipic acid dihydrizide-glutamine.
Cancer is one of the most fatal diseases in the world and it has been years that finding new drugs and chemotherapeutic techniques with lowest side effects become one of the most important challenging matters needs really hard efforts. Chlorambucil (CBL), an ancient direct-acting alkylating anticancer agent, is commonly used for initial treatment of some kinds of cancers but the use of CBL is often limited because of the unpleasant side effects due to its lack of specificity for targeting cancer cells. In this research we tried to increase the specificity of CBL by producing a novel conjugate by using glutamine amino acid (Glut). Based on previous studies, poly amines and nitrogen compounds noticeably are used by cancer cells increasingly; therefore we decided to increase the efficiency and specificity of CBL by designing and producing a novel anti cancer conjugate using glutamine amino acid as an uptake enhancer, CBL, and Adipic acid Dihydrazide (ADH) as a spacer and linker. The biological tests were carried out on HT29 colorectal cancer cell line to evaluate its anticancer properties. Biological tests like MTT assay, finding IC50, evaluating the induced mechanism of the death of our novel CBL-Glutamine conjugate on HT29 cells, testing abnormal toxicity of this conjugate on mice in comparison with CBL drug were careid out. We found that not only CBL-Glutamine conjugate preserved its anti cancer property with regard to CBL drug, but also it represent lower abnormal toxicity in mice. Apoptosis was detected as its mechanism of the death. Our present study provides a promising strategy for targeting cancer cells using amino acids nano-conjugate drugs. The future perspectives have also been highlighted in continuing similar and relative researches.
Department Hepatitis and AIDS Department, Pasteur Institute of Iran, Tehran, Iran and Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. shafieeardestani@gmail.com.
Maryam Akhavan
MA
Tabasi
Massoud
M
Amanlou
Seyed Davar
SD
Siadat
Zahra
Z
Nourmohammadi
Farnoor Davachi
FD
Omoomi
Seyed Esmaeil Sadat
SE
Ebrahimi
Mohammad Reza
MR
Aghasadeghi
Pooneh
P
Rahimi
Sahar
S
Pourhosseini
Bita
B
Mehravi
Mehdi Shafiee
MS
Ardestani
D000272:Adipates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002699:Chlorambucil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005973:Glutamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D058990:Molecular Targeted Therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000272:Adipates; D000970:Antineoplastic Agents; D005973:Glutamine; D002699:Chlorambucil