Abstract |
The present report describes development of a novel, bifunctional molecule possessing both selective antiproliferative activity and siRNA transfection ability. We synthesized a series of cationic lipo- benzamides and screened for in vitro anticancer activities against a panel of cancer and non- cancer cells. The molecule with a ten carbon chain-length (C10M) significantly inhibited proliferation of cancer cells via arresting the cell cycle predominantly in the G1 phase; but did not affect non-cancerous cells. C10M effectively mediated siRNA delivery in vitro. The combined anticancer effect of the delivery of C10M together with its survivin-targeting siRNA cargo was significantly (p < 0.05) superior to that of agent alone. To our knowledge, this is the first report of a dual-purpose molecule with intrinsic anticancer activity and suitability for use in siRNA delivery.
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Authors | Prathap Reddy Muktapuram, Rishi Kumar Gara, Komal Sharma, Chilappa Rohit, Kolupula Srinivas, Durga Prasad Mishra, Surendar Reddy Bathula |
Journal | European journal of medicinal chemistry
(Eur J Med Chem)
Vol. 56
Pg. 400-8
(Oct 2012)
ISSN: 1768-3254 [Electronic] France |
PMID | 22926227
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 Elsevier Masson SAS. All rights reserved. |
Chemical References |
- Antineoplastic Agents
- Benzamides
- RNA, Small Interfering
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Topics |
- Animals
- Antineoplastic Agents
(chemical synthesis, chemistry, pharmacology)
- Apoptosis
(drug effects)
- Benzamides
(chemical synthesis, chemistry, pharmacology)
- COS Cells
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Cell Survival
(drug effects)
- Chlorocebus aethiops
- Dose-Response Relationship, Drug
- Drug Delivery Systems
- Drug Screening Assays, Antitumor
- Gene Silencing
(drug effects)
- Hep G2 Cells
- Humans
- MCF-7 Cells
- Mice
- Models, Molecular
- Molecular Structure
- NIH 3T3 Cells
- RNA, Small Interfering
(genetics, metabolism, pharmacology)
- Structure-Activity Relationship
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