Influence of Solvent Polarity and DNA-Binding on Spectral Properties of Quaternary Benzo[c]phenanthridine Alkaloids

Abstract

Quaternary benzo[c]phenanthridine alkaloids are secondary metabolites of the plant families Papaveraceae, Rutaceae, and Ranunculaceae with anti-inflammatory, antifungal, antimicrobial and anticancer activities. Their spectral changes induced by the environment could be used to understand their interaction with biomolecules as well as for analytical purposes. Spectral shifts, quantum yield and changes in lifetime are presented for the free form of alkaloids in solvents of different polarity and for alkaloids bound to DNA. Quantum yields range from 0.098 to 0.345 for the alkanolamine form and are below 0.033 for the iminium form. Rise of fluorescence lifetimes (from 2–5 ns to 3–10 ns) and fluorescence intensity are observed after binding of the iminium form to the DNA for most studied alkaloids. The alkanolamine form does not bind to DNA. Acid-base equilibrium constant of macarpine is determined to be 8.2–8.3. Macarpine is found to have the highest increase of fluorescence upon DNA binding, even under unfavourable pH conditions. This is probably a result of its unique methoxy substitution at C12 a characteristic not shared with other studied alkaloids. Association constant for macarpine-DNA interaction is 700000 M-1.

Skeleton selectivity in complexation of chelerythrine and chelerythrine-like natural plant alkaloids with the G-quadruplex formed at the promoter of c-MYC oncogene: in silico exploration

“…77 It has been observed that incorporation of methoxy group at 12 th position enhances the anticancer activity of macarpine 78 also, improves its DNA binding. 75 Similarly our observation suggests that substitution of methoxy group at 12 th position of CHE is enhancing the binding affinity towards Pu27.…”

“…12 th position of the benzo[c]phenanthridinium compounds has been found to play crucial role in determining their cytotoxic properties. 72,[75][76][77][78] Mackay et al have reported the inuence of 12-alkoxy group of N-methyl benzo[c] phenanthridinium compounds over their anti cancer activity. They found that non functionalized shorter aliphatic chains as 12-alkoxy group show better anticancer activity.…”

Chelerythrine Chloride is an Affinity-Labeling Inactivator of CYP3A4 by Modification of Cysteine239

“…2,3 QBAs share the same skeleton linking several methoxy-or methylenedioxy-substituents and mostly exist as the iminium form (chloride) in plants of Fumariaceae, Papaveraceae, Ranunculaceae, and Rutaceae. 4,5 Considering the presence of reactive iminium group, these compounds are prone to react with nucleophiles by 1,2-addition. 4 Chelerythrine chloride (CHE, Scheme 1), one of the most representative and commercially available QBAs, is mainly isolated from edible and medicinal plants of greater celandine Chelidonium majus L. and M. cordata.…”

“…4,5 Considering the presence of reactive iminium group, these compounds are prone to react with nucleophiles by 1,2-addition. 4 Chelerythrine chloride (CHE, Scheme 1), one of the most representative and commercially available QBAs, is mainly isolated from edible and medicinal plants of greater celandine Chelidonium majus L. and M. cordata. 5,6 A variety of reported pharmacological properties of CHE include antitumor, antibacterial, antimicrobial, anti-inflammatory, antiplaque, adrenolytic, and local anesthetic effects.…”

Alkaloid Escholidine and Its Interaction with DNA Structures

“…Quaternary protoberberine alkaloids (QPA) represent a large class of isoquinoline alkaloids [ 1 , 2 , 3 , 4 ]. They consist of variations of a tetracyclic ring system, a derivate of 5,6-dihydrodibenzo[ a , g ]quinolizinium [ 5 , 6 , 7 ].…”