Synthesis and evaluation of 2-chloroethylnitrosoureas of substituted naphthalimides as mixed-function anticancer compounds.

PubMed

Samanta, S; Pain, A; Dutta, S; Sanyal, U

2001-01-01

New mixed function anticancer compounds as 2-chloroethylnitrosoureas of substituted naphthalimides represented by bromonap-NU 4a and chloronap-NU 4b, have been synthesized from 4-bromo- and 4-chloro-l,8-naphthalic anhydride, respectively following a 3-step process. Their chemical alkylating activity compared with nor -HN2 indicated that they possess greater alkylating activity than the latter. Their antitumour efficacies were assessed in vivo in two murine ascites tumours, namely Ehrlich ascites carcinoma (EAC) and Sarcoma-180 (S-180) by measuring the increase in median survival times (MST) of drug treated (T) over untreated control (C) mice. Two standard clinical drugs namely endoxan (cyclophosphamide) and 5-fluorouracil (5-FU) were used as positive controls for comparison. Both of them have displayed substantial and reproducible antitumoral activity in these tumours comparable with 5-FU. These were further screened in vitro in 6 different human tumour cell lines but no significant activity was observed in those lines.

Amelioration of cyclophosphamide induced myelosuppression and oxidative stress by cinnamic acid.

PubMed

Patra, Kartick; Bose, Samadrita; Sarkar, Shehnaz; Rakshit, Jyotirmoy; Jana, Samarjit; Mukherjee, Avik; Roy, Abhishek; Mandal, Deba Prasad; Bhattacharjee, Shamee

2012-02-05

Cinnamic acid (C9H8O2), is a major constituent of the oriental Ayurvedic plant Cinnamomum cassia (Family: Lauraceae). This phenolic acid has been reported to possess various pharmacological properties of which its antioxidant activity is a prime one. Therefore it is rational to hypothesize that it may ameliorate myelosuppression and oxidative stress induced by cyclophosphamide, a widely used chemotherapeutic agent. Commercial cyclophosphamide, Endoxan, was administered intraperitoneally to Swiss albino mice (50mg/kg) pretreated with 15, 30 and 60mg/kg doses of cinnamic acid orally at alternate days for 15days. Cinnamic acid pre-treatment was found to reduce cyclophosphamide induced hypocellularity in the bone marrow and spleen. This recovery was also reflected in the peripheral blood count. Amelioration of hypocellularity could be correlated with the modulation of cell cycle phase distribution. Cinnamic acid pre-treatment reduced bone marrow and hepatic oxidative stress as evident by lipid peroxidation and activity assays of antioxidant enzymes such as superoxide dismutase, catalase and glutathione-S-transferase. The present study indicates that cinnamic acid pretreatment has protective influence on the myelosuppression and oxidative stress induced by cyclophosphamide. This investigation is an attempt and is the first of its kind to establish cinnamic acid as an agent whose consumption provides protection to normal cells from the toxic effects of a widely used anti-cancer drug. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.