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Photosensitizing properties and subcellular localisation of 3,4-dihydro-β-carbolines harmaline and harmalol
Photochemical & Photobiological Sciences ( IF 2.7 ) Pub Date : 2022-11-19 , DOI: 10.1007/s43630-022-00328-7
M Paula Denofrio 1, 2 , Jose M Paredes 3 , Juan G Yañuk 1, 2 , Maria D Giron 4 , Rafael Salto 4 , Eva M Talavera 3 , Luis Crovetto 3 , Franco M Cabrerizo 1, 2
Affiliation  

Harmaline (1) and harmalol (2) represent two 3,4-dihydro-β-carboline (DHβCs) most frequently reported in a vast number of living systems. Fundamental aspects including the photosensitizing properties, cellular uptake, as well as the cyto- and phototoxicity of 1 and 2 were investigated herein. The molecular basis underlying the investigated processes are elucidated. Data reveal that both alkaloids show a distinctive pattern of extracellular DNA photodamage. Compound 1 induces a DNA photodamage profile dominated by oxidised purines and sites of base loss (AP sites), whereas 2 mostly induces single-strand breaks (SSBs) in addition to a small extent of purine oxidative damage. In both cases, DNA oxidative damage would occur through type I mechanism. In addition, a concerted hydrolytic attack is suggested as an extra mechanism accounting for the SSBs formation photoinduced by 2. Subcellular internalisation, cyto- and phototoxicity of 1 and 2 and the corresponding full-aromatic derivatives harmine (3) and harmol (4) also showed quite distinctive patterns in a structure-dependent manner. These results are discussed in the framework of the potential biological, biomedical and/or pharmacological roles reported for these alkaloids.

Graphical abstract

The subtle structural difference (i.e., the exchange of a methoxy group for a hydroxyl substituent at C(7)) between harmaline and harmalol, gives rise to distinctive photosensitizing and subcellular localisation patterns.



中文翻译:

3,4-二氢-β-咔啉 harmaline 和 harmalol 的光敏特性和亚细胞定位

Harmaline ( 1 ) 和 harmalol ( 2 ) 代表两种3,4 -二氢-β-咔啉 (DHβCs),在大量生命系统中最常被报道。本文研究了12的光敏特性、细胞摄取以及细胞毒性和光毒性等基本方面。阐明了所研究过程的分子基础。数据显示,这两种生物碱均表现出独特的细胞外 DNA 光损伤模式。化合物1诱导以氧化嘌呤和碱基丢失位点(AP 位点)为主的 DNA 光损伤谱,而2除少量嘌呤氧化损伤外,主要诱导单链断裂 (SSB)。在这两种情况下,DNA 氧化损伤都会通过 I 型机制发生。此外,协同水解攻击被认为是解释2光诱导 SSB 形成的额外机制。12以及相应的全芳香族衍生物 harmine ( 3 ) 和 harmol ( 4 )的亚细胞内化、细胞毒性和光毒性也以结构依赖的方式显示出非常独特的模式。这些结果在报告的这些生物碱的潜在生物学、生物医学和/或药理学作用的框架内进行了讨论。

图形概要

harmaline 和 harmalol 之间的细微结构差异(即 C(7) 处的羟基取代基的甲氧基交换)产生了独特的光敏和亚细胞定位模式。

更新日期:2022-11-20
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