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Purpose: Vinca alkaloids and taxanes are tubuline inhibitors in cancer therapy, whose value is restricted by drug resistance and severe side effects. Novel classes of microtubule-stabilizing agents have been developed, including the myxobacterial epothilones, disorazoles and tubulysins. Methods: The binding of two disorazoles (A1, C3) and five tubulysins (pretubulysin, desmethyltubulysin, tubulysins A, B and D) to tubulin was investigated an in silico molecular docking approach. The results were compared with six epothilones (A-F) as well as vinblastine and paclitaxel as control drugs. Results: Epothilones, disorazoles and tubulysins bound to both the vinblastine and paclitaxel binding sites of tubulin. Tubulysins and disorazoles bound with weaker affinity to tubulins as epothilones did. Epothilones showed binding energies close to that of vinblastine at the vinblastine pharmacophore. Conclusions: These results imply that the paclitaxel binding site, which was thought to be exclusive for microtubule-stabilizing drugs may also bind microtubule-destabilizing agents. This may be explained by the fact that the binding site of paclitaxel extends over regions that are relatively close to those of vinblastine.

EFFECTIVENESS OF HONEY DRESSING AND SILVER SULFADIAZINE DRESSING ON WOUNDS HEALING IN BURN PATIENTS