In vivo chemotherapeutic insight of a novel isocoumarin (3-hexyl-5,7-dimethoxy-isochromen-1-one): Genotoxicity, cell death induction, leukometry and phagocytic evaluation

Abstract Chemotherapy is one of the major approaches for the treatment of cancer. Therefore, the development of new chemotherapy drugs is an important aspect of medicinal chemistry. Chemotherapeutic agents include isocoumarins, which are privileged structures with potential antitumoral activity. Herein, a new 3-substituted isocoumarin was synthesized from 2-iodo-3,5-dimethoxy-benzoic acid and oct-1-yne in a cross-coupling Sonogashira reaction followed by a copper iodide-catalyzed intramolecular cyclization as key step using MeOH/Et3N as the solvent system. The present study also evaluated the leukometry, phagocytic activity, genotoxic potential and cell death induction of three different doses (5 mg/kg, 10 mg/kg and 20 mg/kg) of this newly synthesized isocoumarin, alone and in combination with the commercial chemotherapeutic agents cyclophosphamide (100 mg/kg) and cisplatin (6 mg/kg) in male Swiss mice. The results suggest that the isocoumarin has genotoxicity and causes cell death. Noteworthy, this new compound can increase splenic phagocytosis and lymphocyte frequency, which are related to immunomodulatory activity. When combined with either cyclophosphamide or cisplatin, chemopreventive activity led to a reduction in the effects of both chemotherapeutic drugs. Thus, the new isocoumarin is not a candidate for chemotherapeutic adjuvant in treatments using cyclophosphamide or cisplatin. Nevertheless, the compound itself is an important prototype for the development of new antitumor drugs.

Maternal exposure to Cochlospermum regium: a toxicological evaluation

Cochlospermum regium (Schrank) Pilg., Bixaceae, is a Brazilian plant widely used as a folk medicine in the southwestern of the Brazil to treat inflammation and infection diseases. However, the effects of C. regium hydroethanolic extract on pregnant rats have not been assessed. To evaluate the effects of the C. regium on pregnant rats during the organogenic period, the hydroethanolic extract was administered via gavage at a dose of 11.5 mg/kg/day to rats from 6th to 15th day of pregnancy. No clinical signs of maternal toxicity were observed. The placenta's and fetuses' weight were similar in control and treated animals. The term fetuses dis not present malformations or anomalies although the number of live fetuses and birth rate were significantly decreased. In conclusion, the C. regium hydroethanolic extract is nontoxicant to the pregnant rat although it would be likely to interfere in the progress of the embryofetal development.