Abstract
SummaryThis study provides new information on the cellular effects of 1,3,5-triazine nitrogen mustards with different peptide groups in DLD and Ht-29 human colon cancer cell lines. A novel series of 2,4,6-trisubstituted 1,3,5-triazine derivatives bearing 2-chloroethyl and oligopeptide moieties was designed and synthesized. The most cytotoxic derivative was triazine with an Ala-Ala-OMe substituent on the ring (compound 7b). This compound induced time- and dose-dependent cytotoxicity in the DLD-1 and HT-29 colon cancer cell lines. The triazine derivative furthermore induced apoptosis through intracellular signaling pathway attenuation. Compound 7b may be a candidate for further evaluation as a chemotherapeutic agent against colorectal cancer.
Highlights
Nitrogen mustards (NMs), such as chlorambucil and mechlorethamine, are an extensively investigated and clinically used class of anticancer drugs
The synthesis of new analogues of nitrogen mustards 7a-f containing the 1,3,5-triazine ring substituted with dipeptide residue is a multi-step process (Scheme 1)
Hybrid compounds based on nitrogen mustard 1,3,5-triazine have great therapeutic potential, as confirmed by numerous reports, including our research
Summary
Nitrogen mustards (NMs), such as chlorambucil and mechlorethamine, are an extensively investigated and clinically used class of anticancer drugs They are themselves highly carcinogenic, these bifunctional alkylating agents can be used in the treatment of various cancers and autoimmune diseases [1,2,3,4]. Their mechanism of activity is connected to their ability to cross-link double strands of DNA involving the distal guanine bases in the opposite strand of 5’-GNC sequences, yielding bifunctional DNA lesions. It has been reported that these compounds show inhibitory activity against important enzymes involved in cell proliferation cycles
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