(11aS)-7-Methoxy-8-hydroxy-2,3,5,11aβ-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5-one
Names
[ CAS No. ]:
81307-24-6
[ Name ]:
(11aS)-7-Methoxy-8-hydroxy-2,3,5,11aβ-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5-one
[Synonym ]:
Antibiotic DC 81
DC 81
Biological Activity
[Description]:
Antibiotic DC 81 (DC 81), an antitumor antibiotic produced by Streptomyces species, is a PBD (pyrrolo[2,1-c][1,4]benzodiazepine). Antibiotic DC 81 is potent inhibitor of nucleic acid synthesis. Antibiotic DC 81 can recognize and bind to specific sequences of DNA and form a labile covalent adduct[1][2].
[Related Catalog]:
[In Vitro]
Antibiotic DC 81 shows cytotoxicity against human melanoma cell lines B16, A375, A2058, and RPMI7951, with IC50 values of 4.4 μM, 18.5 μM, 31.0 μM, and 41.5 μM, respectively[1][2]. Antibiotic DC 81 exhibits its biological activity by covalently binding to the N2 of guanine in the minor groove of DNA, via the electrophilic carbinolamine functionality at N10-C11[1]. Antibiotic DC 81 (4 μM, 24 h) induces mitochondria dependent apoptosis[2]. Apoptosis Analysis[2] Cell Line: B16 melanoma cells Concentration: 4 μM Incubation Time: 24 h Result: Induced mitochondria dependent apoptosis.
[In Vivo]
Antibiotic DC 81 (0-10 mg/kg, i.p., at day 4, 7, 10, 13 after tumor cell injection) decreases the tumor burden in tumor-bearing mice, but the Antibiotic DC 81 at 10 mg/kg impairs cardiac muscle enzyme and liver function significantly[2]. Animal Model: Female C57BL/6 mice (8-12 weeks old, B16 cells were injected into the tail veins of mice)[2] Dosage: 0.1, 1, 10 mg/kg Administration: i.p., at day 4, 7, 10, 13 after tumor cell injection Result: Substantially decreased the tumor burden by 20% at 1 mg/kg. DC-81 at 10 mg/kg induced an 8-10-fold increase of GPT and a 6-8-fold increase in CPK, which indicated severe impaired liver function and muscle damage. Did not impair significant renal function as demonstrated by serum creatinine.
[References]
Chemical & Physical Properties
[ Density]:
1.43g/cm3
[ Boiling Point ]:
520.5ºC at 760 mmHg
[ Molecular Formula ]:
C13H14N2O3
[ Molecular Weight ]:
246.26200
[ Flash Point ]:
268.6ºC
[ Exact Mass ]:
246.10000
[ PSA ]:
62.13000
[ LogP ]:
1.09480
[ Index of Refraction ]:
1.675