We have located links that may give you full text access.
JOURNAL ARTICLE
REVIEW
Mitochondria-targeted metformins: anti-tumour and redox signalling mechanisms.
Interface Focus 2017 April 7
Reports suggest that metformin exerts anti-cancer effects in diabetic individuals with pancreatic cancer. Thus, metformin is currently being repurposed as a potential drug in cancer treatment. Studies indicate that potent metformin analogues are required in cancer treatment because of the low bioavailability of metformin in humans at conventional antidiabetic doses. We proposed that improved mitochondrial targeting of metformin by attaching a positively charged lipophilic triphenylphosphonium group will result in a new class of mitochondria-targeted metformin analogues with significantly enhanced anti-tumour potential. Using this approach, we synthesized various mitochondria-targeted metformin analogues with different alkyl chain lengths. Results indicate that the antiproliferative effects increased with increasing alkyl chain lengths (100-fold to 1000-fold). The lead compound, mito-metformin10 , potently inhibited mitochondrial respiration through inhibition of complex I, stimulation of superoxide and hydrogen peroxide formation and activation of AMPK. When used in combination with ionizing radiation, mito-metformin10 acted as a radiosensitizer of pancreatic cancer cells. Because of the 1000-fold-higher potency of mitochondria-targeted metformin10 , therapeutically effective plasma concentrations likely can be achieved in cancer patients.
Full text links
Related Resources
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app