Synthesis and Antimicrobial Activity of 3-Alkoxyjatrorrhizine Derivatives

Abstract

The compounds 3-ethoxy- (2), 3-butoxy- (3), 3-hexyloxy- (4), 3-octyloxy- (5), 3-decyloxy- (6) and 3-dodecyloxyjatrorrhizine chlorides (7) were synthesized and tested for their antimicrobial activity in vitro to evaluate structure-activity relationships. Substitution of the H with alkyl groups at C-3-OH led to significant changes in the antimicrobial activity. The antimicrobial activity of the substituted derivatives was 32 - 1000 times higher than that of jatorrhizine (1), which increased as the aliphatic chain was elongated and then decreased slightly when the alkyl chain exceeded eight carbon atoms. 3-Octyloxyjatrorrhizine (5) displayed the highest antimicrobial activity of all compounds. The LD₅₀ values of compounds 1 - 7 were more than 6000 mg/kg body weight, showing a low toxicity. The toxicities of compounds 2 - 7 were slightly lower than that of (1).

Key words

Coptis chinensis Franch. - Ranunculaceae - jatrorrhizine - 3-alkoxyjatrorrhizine derivatives - antimicrobial activity - acute toxicity

References

• 1 Yuan L J, Tu D W, Ye X L, Wu J P. Hypoglycemic and hypocholesterolemic effects of Coptis chinensis Franch inflorescence.  Plant Foods Hum Nutr. 2006;  61 139-44
• 2 Grycová L, Dostál J, Marek R. Quaternary protoberberine alkaloids.  Phytochemistry. 2007;  68 150-75
• 3 Yu Y, Yi Z B, Liang Y Z. Main antimicrobial components of Tinospora capillipes, and their mode of action against Staphylococcus aureus.  FEBS Lett. 2007;  581 179-83
• 4 Fu Y, Hu B R, Tang Q, Fu Q, Xiang J ZH. Hypoglycemic activity of jatrorrhizine.  J Huazhong Univ Sci Technol Med Edition. 2005;  25 491-3
• 5 Han H, Fang D C. The blocking and partial agonistic actions of jatrorrhizine on alpha-adrenoceptors.  Acta Pharmacol Sin. 1989;  18 85-9
• 6 Racková L, Májeková M, Kostálová D, Stefek M. Antiradical and antioxidant activities of alkaloids isolated from Mahonia aquifolium structural aspects.  Bioorg Med Chem. 2004;  12 4709-15
• 7 Volleková A, Koštálova′ D, Kettmann V, Tóth J. Antifungal sctivity of Mahonia aquifolium extract and its major protoberberine alkaloids.  Phytother Res. 2003;  17 834-7
• 8 Iwasa K, Nishiyama Y, Ichimaru M, Moriyasu M, Kim H -S, Wataya Y. et al . Structure-activity relationships of quaternary protoberberine alkaloids having an antimalarial activity.  Eur J Med Chem. 1999;  34 1077-83
• 9 Iwasa K, Kamigauchi M, Sugiura M, Nanba H. Antimicrobial activity of some 13-alkyl-substituted protoberberinium salts.  Planta Med. 1991;  63 196-8
• 10 Iwasa K, Lee D U, Kang S I, Wiegrebe W. Antimicrobial activity of 8-alkyl-and 8-phenyl-substiuted berberines and their 12-bromo derivatives.  J Nat Prod. 1998;  61 1150-3
• 11 Iwasa K, Kamigauchi M, Ueki M, Taniguchi M. Antibacterial activity and structure-activity relationships of berberine analogs.  Eur J Med Chem. 1996;  31 69-78
• 12 Yang Y, Ye X L, Li X G, Zheng J, Zhang B S, Yuan L J. Synthesis and antimicrobial activity of 3-alkoxyjatrorrhizine derivatives.  Planta Med. 2007;  73 602-4
• 13 Ye X L, Li X G, Yuan L J, He H M. Effect of the surface activity on the antibacterial activity of octadecanoyl acetal sodium sulfite series.  Colloids Surf A Physicochem Eng Asp. 2005;  268 5-9
• 14 Ye X L, Li X G, Yuan L J, Ge L H, Zhang B S, Zhou S B. Interaction of houttuyfonate homoligues with the cell membrane of Gram-positive and Gram-negative bacteria.  Colloids Surf A Physicochem Eng Asp. 2007;  301 412-8
• 15 Feng Y M, Xun K M. Extraction of jatrorrhizine chloride from the mother liquid of producing berberine chloride.  China J Chin Mater Med. 1989;  14 29-30
• 16 Ma X R. Drug microbial test handbook. Beijing; People Health Publishing House 2001: 50-3
• 17 Zhou L G. Drug toxicology. Beijing; People’s Medical Publishing House 2003: 59-161
• 18 GB 5193.3 - 2003. Acute toxicity test. Beijing; Standards Press of China 2005: 1-15