Novel ferrocenic steroidal drug derivatives and their bioactivities.
Seven novel ferrocenic derivatives, compounds 1-7, were synthesized from steroidal drugs by Aldol condensation reaction. The derivatives were purified by chromatography, and their structures were determined on the basis of HR-ESI-MS and two-dimensional NMR spectroscopy. The purity of all derivatives was more than 95%. Compounds 1-5 demonstrated anti-proliferative activity on HeLa cell line by SRB assay more than their parent compounds. All seven derivatives showed anti-oxidative activities evaluated by DPPH scavenging and metal ion chelating, while their parent compounds gave no activity. Compound 1 indicated the most potent anti-proliferative activity similar to doxorubicin, with the GI(50) at 0.223 +/- 0.014 microg/mL. Compounds 6 and 7 demonstrated similar potent in vivo anti-inflammatory to their parent compounds (prednisolone and hydrocortisone) at 80.99 +/- 13.5 and 68.24 +/- 10.4% edema inhibition, respectively. This study has suggested that the novel compound 1 was the most potential derivative that can be further developed for cancer treatment.
Manosroi
Jiradej
J
Division of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand. pmpti006@chiangmai.ac.th
Rueanto
Kanjana
K
Boonpisuttinant
Korawinwich
K
Manosroi
Worapaka
W
Biot
Christophe
C
Akazawa
Hiroyuki
H
Akihisa
Toshihiro
T
Issarangporn
Witchapong
W
Manosroi
Aranya
A
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000975:Antioxidants / Q000138:chemical synthesis / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D004487:Edema / Q000188:drug therapy; D005296:Ferrous Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007502:Iron Chelating Agents / Q000138:chemical synthesis / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D000075163:Metallocenes; D010851:Picrates / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization; D013256:Steroids / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D000975:Antioxidants; D001713:Biphenyl Compounds; D005296:Ferrous Compounds; D016166:Free Radical Scavengers; D007502:Iron Chelating Agents; D000075163:Metallocenes; D010851:Picrates; D013256:Steroids; C004931:1,1-diphenyl-2-picrylhydrazyl; C004998:ferrocene