Biological evaluation and mechanism of action of anticancer beta-lactams

ORGN 99

Bimal K. Banik, banik@panam.edu1, Indrani Banik2, and Frederick F. Becker2. (1) Department of Chemistry, The University of Texas-Pan American, 1201 West University Drive, Edinburg, TX 78541, (2) Department of Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030

We are aware from the literature that conformationally constrained molecules often have a greater effect on biological properties when compared to the relatively flexible open-chain compounds.  On the basis of this hypothesis, we anticipated that conformationally constrained analogues of our open chain diamides may increase potency.  Structures 1 and 2 suggest that a ring formation using N1 and C4 would result in b-lactam 3.  With regard to the above, we envisioned that b-lactam 3 of the general structure would serve as a conformationally constrained analogue of our open-chain compounds (1 and 2) that have been shown to have anticancer activity.  In this paper, the biological evaluation and mechanism of action of our anticancer b-lactams related to 3 will be discussed.