Design, synthesis, and bioactivity of putative tubulin ligands with adamantane core.
Several adamantane-based taxol mimetics were synthesized and found to be cytotoxic at micromolar concentrations and to cause tubulin aggregation. The extent of the aggregation is maximal for N-benzoyl-(2R,3S)-phenylisoseryloxyadamantane (5) and is very sensitive to the structural modifications. A hybrid compound (15), combining adamantane-based taxol mimetic with colchicine was synthesized and found to possess both microtubule depolymerizing and microtubule bundling activities in A549 human lung carcinoma cells.
Zefirova
Olga N
ON
Department of Chemistry, M. V. Lomonosov Moscow State University, 119992 Moscow, Russian Federation. olgaz@org.chem.msu.ru
Nurieva
Evgeniya V
EV
Lemcke
Heiko
H
Ivanov
Andrei A
AA
Shishov
Dmitrii V
DV
Weiss
Dieter G
DG
Kuznetsov
Sergei A
SA
Zefirov
Nikolay S
NS
D000218:Adamantane / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002417:Cattle; D003078:Colchicine / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D018716:Molecular Mimicry; D017239:Paclitaxel / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism*
D000972:Antineoplastic Agents, Phytogenic; D014404:Tubulin; D017239:Paclitaxel; D000218:Adamantane; D003078:Colchicine