A novel antitumor compound, N-beta-dimethyl-aminoethyl 9-carboxy-5-hydroxy-10-methoxybenzo[a]-
phenazine-6-carboxamide
sodium salt (NC-190) was evaluated for its antitumor activity in experimental murine
tumor systems. In the initial studies with
P388 leukemia (i.p.-i.p.),
NC-190 led to an increase of greater than 200% in life span (ILS), and 75% of the mice were alive on day 30, when the optimal dose (50 mg/kg, days 1-5) was given. Additionally, the compound had significant activities against i.p. inoculated mouse
L1210 leukemia,
B16 melanoma, M5076
reticulum cell sarcoma,
sarcoma 180, mouse
hepatoma MH134, and rat
Yoshida sarcoma and Yoshida
ascites hepatoma AH130. The optimal dose resulted in a greater than 280% ILS with a 30-day survival of 50% in mice with
L1210 leukemia (100 mg/kg, days 1-5), a 156% ILS in mice with
B16 melanoma (50 mg/kg, days 1-5), a 98% ILS with a 90-day survival of 25% in mice with M5076
reticulum cell sarcoma (25 mg/kg, days 1, 5, 9, and 13), a greater than 300% ILS with a 60-day survival of 50% in mice with
sarcoma 180 (50 mg/kg, days 3-10), a 148% ILS with a 60-day survival of 25% in mice with MH134 (25 mg/kg, days 1-5), a 129% ILS with a 60-day survival of 12.5% in rats with
Yoshida sarcoma (12.5 mg/kg, day 3-10), and a greater than 161% ILS with a 60-day survival of 50% in rats with AH130 (6.3 mg/kg, days 3-10). In the experiments with s.c. inoculated
tumors,
NC-190 not only inhibited
tumor growth, but also increased the life span of mice with
Lewis lung carcinoma or
B16 melanoma. The 60-day survivors accounted for 60% and 30% in mice with
Lewis lung carcinoma and
B16 melanoma, respectively. The compound significantly inhibited the spontaneous lung
metastasis of
Lewis lung carcinoma by more than 90% when eight daily i.v.
injections were given.
NC-190 was active by the i.p., s.c., and i.v. routes. Five consecutive daily i.p. doses (days 1-5) were more effective than a single dose (day 1), two doses (days 1 and 5), or three doses (days 1, 5, and 9).
NC-190 warrants further study as a potential
antineoplastic agent against human
neoplasms, as it has a broad spectrum of antitumor activity and inhibits
metastasis.