Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells
2016
Аутори:
Dinić, JelenaNovaković, Miroslav
Podolski-Renić, Ana
Vajs, Vlatka
Tešević, Vele
Isaković, Aleksandra
Pešić, Milica
Тип документа:
Чланак у часопису (Рецензирана верзија)
Метаподаци
Приказ свих података о документуАпстракт:
Diarylheptanoids represent a group of plant secondary metabolites that possess multiple biological properties and are increasingly recognized for their therapeutic potential. A comparative study was performed on structurally analogous diarylheptanoids isolated from the bark of green (Alnus viridis) and black alder (Alnus glutinosa) to address their biological effects and determine structure-activity relationship. The structures and configurations of all compounds were elucidated by NMR, HR-ESI-MS, UV and IR. Diarylheptanoids actions were studied in human non-small cell lung carcinoma cells (NCI-H460) and normal keratinocytes (HaCaT). A. viridis compounds 3v, 5v, 8v and 9v that possess a carbonyl group at C-3 were considerably more potent than compounds without this group. A. viridis/A. glutinosa analogue pairs, 5v/5g and 9v/9g, which differ in the presence of 3' and 3″-OH groups, were evaluated for anticancer activity and selectivity. 5v and 9v that do not possess 3' and 3″-OH groups showed significantly higher cytotoxicity compared to analogues 5g and 9g. In addition, these two A. viridis compounds induced a more prominent apoptosis in both cell lines and an increase in subG0 cell cycle phase, compared to their A. glutinosa analogues. 5v and 9v treatment triggered intracellular superoxide anion accumulation and notably decreased mitochondrial transmembrane potential. In HaCaT cells, 9v and 9g with a 4,5 double bond caused a more prominent loss of mitochondrial transmembrane potential compared to 5v and 5g which possess a 5-methoxy group instead. Although green alder diarylheptanoids 5v and 9v displayed higher cytotoxicity, their analogues from black alder 5g and 9g could be more favorable for therapeutic use since they were more active in cancer cells than in normal keratinocytes. These results indicate that minor differences in the chemical structure can greatly influence the effect of diarylheptanoids on apoptosis and redox status and determine their selectivity towards cancer cells.
Напомена:
This is a post-peer-review, pre-copyedit version of article: Dinić J, Novaković M, Podolski-Renić A, Vajs V, Tešević V, Isaković A, Pešić M. Structural differences in diarylheptanoids analogues from alnus viridis and alnus glutinosa influence their activity and selectivity towards cancer cells. Chem -Biol Interact. 2016;249:36-45. The final authenticated version is available online at: http://dx.doi.org/10.1016/j.cbi.2016.02.019
Realted to: https://radar.ibiss.bg.ac.rs/handle/123456789/2535.
Кључне речи:
Diarylheptanoids; Mitochondrial transmembrane potential; Reactive oxygen species; Structure-activity relationshipИзвор:
Chemico-Biological Interactions, 2016, 249, 36-45Финансирање / пројекти:
- Идентификација молекуларних маркера за предикцију прогресије тумора, одговора на терапију и исхода болести (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41031)
- Биоактивни природни производи самониклих, гајених и јестивих биљака: одређивање структура и активности (RS-MESTD-Basic Research (BR or ON)-172053)
DOI: 10.1016/j.cbi.2016.02.019
ISSN: 00092797
PubMed: 26944434
WoS: 000372404800005
Scopus: 2-s2.0-84960351174
URI
https://www.sciencedirect.com/science/article/pii/S0009279716300552https://radar.ibiss.bg.ac.rs/123456789/3876