Abstract
Background: Many drugs when conjugated with DNA by covalent or noncovalent interaction form highly reactive, site specific delivery species called drug-DNA adduct.
Objective: The objective of the present review is to highlight the importance and utility of DNA – drug conjugates for site-specific delivery in anti-cancer therapy. Results: Drugs, such as doxorubicin, cisplatin, ellipticine, melphalan, tamoxifen, etc. were reacted with endosomal formaldehyde to form an intermediate Schiff base. The Schiff base can successfully interact with the exocyclic amino group of guanine nucleotides, resulting in drug-DNA adducts through the aminal linkage. This mechanism has been extended to in vitro adduct formation of anthracycline drugs with deoxyguanosine group of DNA, which is highly stable at low temperature and in physiological pH. Conclusion: The adduct would gradually release the drug at a physiological temperature and is thus well suited for site-specific targeted drug delivery with reduced side effects.Keywords: Drug conjugated DNA, deoxyguanosine, doxorubicin, guanine residue, site-specific, targeting.
Graphical Abstract
Current Pharmacogenomics and Personalized Medicine
Title:DNA-drug Conjugates for Site-specific Delivery in Anti-cancer Therapy
Volume: 14 Issue: 2
Author(s): Karimpanakkal C. Ajithkumar and Kannissery Pramod*
Affiliation:
- College of Pharmaceutical Sciences, Govt. Medical College, Kozhikode – 673008, Kerala,India
Keywords: Drug conjugated DNA, deoxyguanosine, doxorubicin, guanine residue, site-specific, targeting.
Abstract: Background: Many drugs when conjugated with DNA by covalent or noncovalent interaction form highly reactive, site specific delivery species called drug-DNA adduct.
Objective: The objective of the present review is to highlight the importance and utility of DNA – drug conjugates for site-specific delivery in anti-cancer therapy. Results: Drugs, such as doxorubicin, cisplatin, ellipticine, melphalan, tamoxifen, etc. were reacted with endosomal formaldehyde to form an intermediate Schiff base. The Schiff base can successfully interact with the exocyclic amino group of guanine nucleotides, resulting in drug-DNA adducts through the aminal linkage. This mechanism has been extended to in vitro adduct formation of anthracycline drugs with deoxyguanosine group of DNA, which is highly stable at low temperature and in physiological pH. Conclusion: The adduct would gradually release the drug at a physiological temperature and is thus well suited for site-specific targeted drug delivery with reduced side effects.Export Options
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Cite this article as:
Ajithkumar C. Karimpanakkal and Pramod Kannissery*, DNA-drug Conjugates for Site-specific Delivery in Anti-cancer Therapy, Current Pharmacogenomics and Personalized Medicine 2016; 14 (2) . https://dx.doi.org/10.2174/1875692115666170208121925
DOI https://dx.doi.org/10.2174/1875692115666170208121925 |
Print ISSN 1875-6921 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6913 |
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