Synthesis, characterization and antitumor mechanism investigation of ruthenium(II) polypyridyl complexes with artesunate moiety
Six artesunate (ART) conjugated ruthenium(II) complexes (Ru(II)-ART conjugates) with the formula [Ru(N^N) 2 bpy(4-CH 3 -4′-CH 2 OART)](PF 6 ) 2 ( Ru-ART-1-3 ) and [Ru(N^N) 2 bpy(4-CH 2 OART-4′-CH 2 OART)](PF 6 ) 2 ( Ru-ART-4 – 6 ) (N^N = 2,2′-bipyridine (bpy, in Ru-ART-1 and Ru-ART-4 ), 1,10-phenant...
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| Published in: | Journal of biological inorganic chemistry 2021-12, Vol.26 (8), p.909-918 |
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| Main Authors: | , , , , , |
| Format: | Article |
| Language: | eng |
| Subjects: | |
| Online Access: | Get full text |
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| Summary: | Six artesunate (ART) conjugated ruthenium(II) complexes (Ru(II)-ART conjugates) with the formula [Ru(N^N)
2
bpy(4-CH
3
-4′-CH
2
OART)](PF
6
)
2
(
Ru-ART-1-3
) and [Ru(N^N)
2
bpy(4-CH
2
OART-4′-CH
2
OART)](PF
6
)
2
(
Ru-ART-4
–
6
) (N^N = 2,2′-bipyridine (bpy, in
Ru-ART-1
and
Ru-ART-4
), 1,10-phenanthroline (phen, in
Ru-ART-2
and
Ru-ART-5
) and 4,7-diphenyl-1,10-phenanthroline (DIP, in
Ru-ART-3
and
Ru-ART-6
)), were synthesized and characterized. Among them,
Ru-ART-1-3
and
Ru-ART-4-6
carry one and two ART moieties, respectively.
Ru-ART-3
and
Ru-ART-6
exhibit better cytotoxicity among six Ru(II)-ART conjugates. These two complexes can be effectively taken up by human cervical carcinoma (HeLa) cells. In addition, they selectively kill cancer cell lines while mildly affect normal cells. Mechanism studies have shown that HeLa cells treated with
Ru-ART-3
and
Ru-ART-6
show typical apoptotic characteristics (morphology changes, mitochondrial dysfunction, caspase cascade, etc.). On the other hand, the up regulation of Beclin-1 and conversion of LC3-I to LC3-II note the appearance of autophagy. As a result,
Ru-ART-3
and
Ru-ART-6
induce autophagy-dependent cell apoptosis via mitochondrial dysfunction and reactive oxygen species (ROS) accumulation.
Graphic abstract
In this work, six artesunate (ART) conjugated ruthenium(II) complexes (Ru(II)-ART conjugates) have been synthesized and characterized. Among them,
Ru-ART-3
and
Ru-ART-6
exhibit better cytotoxicity. Mechanism studies have shown that HeLa cells treated with
Ru-ART-3
and
Ru-ART-6
show typical apoptotic characteristics (morphology changes, mitochondrial dysfunction, caspase cascade, etc.). On the other hand, the up regulation of Beclin-1 and conversion of LC3-I to LC3-II note the appearance of autophagy |
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| ISSN: | 0949-8257 1432-1327 |