|Catalog||Product Name||CAS Number||Molecular Formula||Molecular Weight|
|BADC-00811||Duocarmycin DM (free base)||1116745-06-2||C26H26ClN3O3||463.96 g/mol|
Since the first anthracycline anticancer drug Daunorubicins (DNRs) were isolated in 1957, anthracycline antibiotics have become one of the most effective chemotherapeutic drugs widely used in clinic. The anthracycline antibiotics, of which Daunorubicins (Daunomycin) and Doxorubicins (Adriamycin, DOXs) are the parent compounds, are widely used in cancer chemotherapy. As an anti-tumor antibiotic, Daunorubicins are the first-line drug for the treatment of acute leukemia, chronic myeloid leukemia, malignant lymphoma, non-small cell lung cancer, breast cancer. Doxorubicins were isolated from Str. peucetius var. caesius in 1969, which has strong anticancer activity and high chemotherapy index. Research have shown that there is a close relationship between the intercalation of anthracycline drugs into DNA strand and their anticancer activity. Daunorubicins and Doxorubicins are arguably the best characterized DNA intercalators. These compounds are important models for understanding how small molecules interact with DNA in a sequence-specific manner.
Anthracycline antibiotics are composed of a tetracyclic chromophore (glycosidic ligand) linked to one or more glycosyl or glucosamine through glycosidic bonds. Different anthracyclines have different ligands or glycosyls. The structure of Doxorubicins is very similar to Daunorubicins, that is, the H atom at 14 C of Daunorubicins replaced by OH to obtain Doxorubicins. Therefore, Doxorubicins can also be prepared by chemical synthesis of Daunorubicins.
The mechanism of anthracycline antibiotics indicated that anthraquinone rings were inserted and paralleled between the base pairs of double-stranded DNA by non-specific insertion, thus forming a relatively stable anthracene ring-DNA complex. The long axis of anthracycline is basically perpendicular to the hydrogen bond of the base pair, and the amino group of the glucosamine is combined with the phosphate group of DNA by ionic bond. This embedding effect changes the distance between the base pairs, thus changing the template properties of DNA. Changes in nucleic acid structure inhibit DNA replication and RNA transcription and affect the proliferation of rapidly growing tumor cells.
Furthermore, anthracyclines are also involved in the redox process to generate free radicals and eventually form reactive oxygen species fragments (O-, -OH, 1O2, etc.). These fragments are very active and directly act on biological targets (DNA, cell membrane, etc.) without protein-mediated, which play a special role in destroying the structure and function of biological targets.
The anticancer mechanism of Daunorubicins is mainly that it can produce daunorubicinol through liver metabolism, which changes the DNA topology by embedding the DNA base pairs of cancer cells. It affects gene expression by inhibiting the activity of DNA polymerase and damaging DNA, so as to kill tumor cells and treat cancer.
Doxorubicins are cell cycle non-specific drug. It is mainly inserted between DNA base pairs and tightly bound to DNA, thereby preventing DNA replication, inhibiting the role of DNA-dependent polymerase and interfering with RNA transcription. This effect of preventing cell division cannot selectively distinguish tumor cells from normal cells, so as most chemotherapy drugs, Doxorubicins have many adverse reactions.
At present, the classic scheme for clinical treatment of acute myeloid leukemia (AML) is anthracycline combined with cytarabine (Ara-C). The clinical complete remission rate of AML (except M3) treated with cytarabine combined with anthracyclines is about 80%-90%. The clinical complete remission rate of Daunorubicins combined with cytarabines in the treatment of AML was about 65.0%. In recent years, with the increasing binding capacity of DNA to idarubicin (IDA) and its less toxic side effects on human heart, IDA has been widely used in clinical treatment.
To reduce cardiac toxicity, Doxorubicins is mainly used in combination with liposomes for clinical application. At present, two kinds of Doxorubicins-liposomes drugs were listed abroad. That is, polyethylene glycol (PEG) modified long-acting circulating liposomes (PLD) and non-PEG modified conventional liposomes (NPLD). PEG-modified Doxorubicins-liposomes are mainly used in the treatment of recurrent ovarian cancer and AIDS-related Kaposi’s. However, non-PEG modified Doxorubicins-liposomes are widely used in the treatment of metastatic breast cancer.