New synthetic marine alkaloid analogs with anticancer activity
Cancer is one of the leading causes of death in the world. Therefore new improved chemotherapeutic agents are needed. The tambjamines are a class of marine alkaloids with intriguing pharmacological properties, including antitumor activity. Inspired in the structure of these compounds we have synthesized a family of synthetic analogs displaing interesting antitumor activity in vitro, promoting apoptosis in several cancer cell lines.
The compounds described in this invention display interesting antitumor activity in vitro showing low toxicity against normal cells. Their action mechanism is proposed to be their ionophoric activity. These compounds can function as anion carriers upsetting the ionic balance of cells. They are cytotoxic and through thios activity they induce apoptosis indifferent cellular cancell lines.
The compounds described in this invention are inspired by the structure of marine alkaloid bearing a 4-methoxybipyrrol unit. Substitution of this moiety by different enamine group yields the active derivatives. These compounds can promote the transmembrane transport of anions such as chloride and bicarbonate.The ionophoric activity of these compounds changes the intracelular pH of the treated cells. Vital tinction assays using acrinidine orange revealed the deacidification of acidic organelles such as lysosomes. It is known that this process triggers apoptosis and IC50 values in the low micromolar range were calculated for these compounds in diferent cancer cell lines.
The mechanism of action of these compounds allows them to be used in resistant cell lines against conventional chemotherapies.
These compounds should be of interest for pharmaceutilcal companies willing to conduct preclinical studies to assess their potential in the clinic. They can be used for the treatment of different cancer conditions.
Jose Manuel López López
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