Synthesis and anti-cancer activity of chiral tetrahydropyrazolo[1,5-a]pyridine-fused steroids.
Regio- and stereoselective synthesis of novel chiral 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused steroids via [8π+2π] cycloaddition of diazafulvenium methides with steroidal scaffolds is reported. The biological evaluation of the new family of hexacyclic steroids as anti-cancer agents was also carried out. Hexacyclic steroids bearing a benzyl group at C-22, derived from 16-dehydropregnenolone and 16-dehydroprogesterone, show considerable cytotoxicity against EL4 (murine T-lymphoma) in contrast with the corresponding C-22-unsubstituted derivatives showing low cytotoxicity. Thus, results indicate that the presence of the benzyl group is important to ensure cytotoxicity.
CQC and Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal.
Susana M M
SMM
Lopes
CQC and Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal.
Emanuel P
EP
Sousa
CCMAR - Centre of Marine Sciences, University of Algarve, Ed. 7, Campus de Gambelas, 8005-139 Faro, Portugal.
Luísa
L
Barreira
CCMAR - Centre of Marine Sciences, University of Algarve, Ed. 7, Campus de Gambelas, 8005-139 Faro, Portugal.
Cátia
C
Marques
CCMAR - Centre of Marine Sciences, University of Algarve, Ed. 7, Campus de Gambelas, 8005-139 Faro, Portugal.
Maria João
MJ
Rodrigues
CQC and Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal. Electronic address: tmelo@ci.uc.pt.
Teresa M V D
TMVD
Pinho E Melo
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D051379:Mice; D011725:Pyridines / Q000737:chemistry*; D013237:Stereoisomerism; D013256:Steroids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D011725:Pyridines; D013256:Steroids
Anti-cancer activity; Cycloadditions; Extended dipoles; Microwave chemistry; Sigmatropic shifts; Steroids