ABSTRACT
A graph-theoretical method is applied to model of the relations between structure and biological activity of the anticancer Pt(II) complexes. Values of LD50, ID90, TI and % of ILS resulted from the treatment of animals bearing experimentalis ADJ/PC6 or L1210 tumors, available in the literature, were used as parameters characterizing the antitumor activity of platinum complexes. The results indicate that it is possible to find a topological description of these complexes which could be useful in their structure - activity investigations.
Subject(s)
Platinum/chemistry , Platinum/pharmacology , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Chemical Phenomena , Chemistry, Physical , Neoplasms, Experimental/drug therapy , Structure-Activity RelationshipABSTRACT
Conformation space near the crystal conformations of proline-containing cyclic octapeptides and cyclic hexapeptides of C2 sequence symmetry, e.g. cyclo-(Gly-Pro-D-Phe)2 and cyclo-(D-Ala-Gly-Pro-D-Phe)2, was explored using molecular mechanics. Conformations found in crystals were energy minimized, distortions were introduced by systematically fixing backbone dihedral angles at individual residues, and nearby energy-minimized conformations were then located. Interatomic distances and dihedral angles were examined in the conformations within a few kilocalories of the most stable conformation. A common form of flexibility was found to involve libration of amide planes. Among the peptides examined, the cyclic hexapeptides were found to have greater freedom than the cyclic octapeptides, and cyclo-(D-Ala-Gly-Pro-D-Phe)2 was found to be more rigid than cyclo-(D-Ala-Gly-Pro-Phe)2.
