BIOMAT Database Logo BIOMAT Database Logo

Design, Synthesis, and in Vitro Biological Evaluation of 14-Hydroxytylophorine-dichloroacetate Co-drugs as Antiproliferative Agents. 2019

Ziad Omran, and Mohamed Alarja, and Ashraf N Abdalla, and Munjed M Ibrahim, and Mohammad A Hossain, and Linwei Chen, and Yuxiu Liu, and Qingmin Wang
College of Pharmacy, Umm Al-Qura University.

Co-drug, or mutual-prodrug, is a drug design approach consisting of covalently linking two active drugs so as to improve the pharmacokinetics and/or pharmacodynamics properties of one or both drugs. Co-drug strategy has proven good success in overcoming undesirable properties such as absorption, poor bioavailability, nonspecificity, and gastrointestine tract (GIT) side effects. In this work, we successfully developed a co-drug of 14-hydroxytylophorine, a phenanthroindolizidine derivative with remarkable antiproliferative activity, and dichloroacetate, a known inhibitor of pyruvate dehydrogenase kinase. Dichloroacetate steers tumour cell metabolism from glycolysis back to glucose oxidation, which in turn reverses the Warburg effect and renders tumour cells with a proliferative disadvantage. The obtained co-drugs retained the cytotoxicity of 14-hydroxytylophorine. However, they showed similar unselectivity towards normal cells.

UI MeSH Term Description Entries
D007211 Indoles Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D010616 Phenanthrenes POLYCYCLIC AROMATIC HYDROCARBONS composed of three fused BENZENE rings.
D011355 Prodrugs A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug. Drug Precursor,Drug Precursors,Pro-Drug,Prodrug,Pro-Drugs,Precursor, Drug,Precursors, Drug,Pro Drug,Pro Drugs
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D003412 Cricetulus A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research. Hamsters, Armenian,Hamsters, Chinese,Hamsters, Grey,Armenian Hamster,Armenian Hamsters,Chinese Hamster,Chinese Hamsters,Grey Hamster,Grey Hamsters,Hamster, Armenian,Hamster, Chinese,Hamster, Grey
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004354 Drug Screening Assays, Antitumor Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals. Anticancer Drug Sensitivity Tests,Antitumor Drug Screens,Cancer Drug Tests,Drug Screening Tests, Tumor-Specific,Dye Exclusion Assays, Antitumor,Anti-Cancer Drug Screens,Antitumor Drug Screening Assays,Tumor-Specific Drug Screening Tests,Anti Cancer Drug Screens,Anti-Cancer Drug Screen,Antitumor Drug Screen,Cancer Drug Test,Drug Screen, Anti-Cancer,Drug Screen, Antitumor,Drug Screening Tests, Tumor Specific,Drug Screens, Anti-Cancer,Drug Screens, Antitumor,Drug Test, Cancer,Drug Tests, Cancer,Screen, Anti-Cancer Drug,Screen, Antitumor Drug,Screens, Anti-Cancer Drug,Screens, Antitumor Drug,Test, Cancer Drug,Tests, Cancer Drug,Tumor Specific Drug Screening Tests
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy

Related Publications

Ziad Omran, and Mohamed Alarja, and Ashraf N Abdalla, and Munjed M Ibrahim, and Mohammad A Hossain, and Linwei Chen, and Yuxiu Liu, and Qingmin Wang
Naphthoflavones as Antiproliferative Agents: Design, Synthesis and Biological Evaluation.
January 2016, Anti-cancer agents in medicinal chemistry,
Ziad Omran, and Mohamed Alarja, and Ashraf N Abdalla, and Munjed M Ibrahim, and Mohammad A Hossain, and Linwei Chen, and Yuxiu Liu, and Qingmin Wang
Design, Synthesis and Biological Evaluation of Steroidal Glycoconjugates as Potential Antiproliferative Agents.
May 2021, ChemMedChem,
Ziad Omran, and Mohamed Alarja, and Ashraf N Abdalla, and Munjed M Ibrahim, and Mohammad A Hossain, and Linwei Chen, and Yuxiu Liu, and Qingmin Wang
Design, synthesis, and biological evaluation of artemisinin-indoloquinoline hybrids as potent antiproliferative agents.
November 2014, Molecules (Basel, Switzerland),
Ziad Omran, and Mohamed Alarja, and Ashraf N Abdalla, and Munjed M Ibrahim, and Mohammad A Hossain, and Linwei Chen, and Yuxiu Liu, and Qingmin Wang
Design, synthesis and biological evaluation of novel steroidal spiro-oxindoles as potent antiproliferative agents.
May 2014, The Journal of steroid biochemistry and molecular biology,
Ziad Omran, and Mohamed Alarja, and Ashraf N Abdalla, and Munjed M Ibrahim, and Mohammad A Hossain, and Linwei Chen, and Yuxiu Liu, and Qingmin Wang
New cinnamic acid-pregenolone hybrids as potential antiproliferative agents: Design, synthesis and biological evaluation.
December 2019, Steroids,
Ziad Omran, and Mohamed Alarja, and Ashraf N Abdalla, and Munjed M Ibrahim, and Mohammad A Hossain, and Linwei Chen, and Yuxiu Liu, and Qingmin Wang
Design, synthesis and biological evaluation of new steroidal β-triazoly enones as potent antiproliferative agents.
October 2019, Steroids,
Ziad Omran, and Mohamed Alarja, and Ashraf N Abdalla, and Munjed M Ibrahim, and Mohammad A Hossain, and Linwei Chen, and Yuxiu Liu, and Qingmin Wang
Design, Synthesis, and Biological Evaluation of Indole-2-carboxamides as Potential Multi-Target Antiproliferative Agents.
July 2023, Pharmaceuticals (Basel, Switzerland),
Ziad Omran, and Mohamed Alarja, and Ashraf N Abdalla, and Munjed M Ibrahim, and Mohammad A Hossain, and Linwei Chen, and Yuxiu Liu, and Qingmin Wang
Design, synthesis, biological and in silico evaluation of coumarin-hydrazone derivatives as tubulin targeted antiproliferative agents.
October 2019, Bioorganic chemistry,
Ziad Omran, and Mohamed Alarja, and Ashraf N Abdalla, and Munjed M Ibrahim, and Mohammad A Hossain, and Linwei Chen, and Yuxiu Liu, and Qingmin Wang
Synthesis and Biological Evaluation of Amino Chalcone Derivatives as Antiproliferative Agents.
November 2020, Molecules (Basel, Switzerland),
Ziad Omran, and Mohamed Alarja, and Ashraf N Abdalla, and Munjed M Ibrahim, and Mohammad A Hossain, and Linwei Chen, and Yuxiu Liu, and Qingmin Wang
Design, synthesis, and biological evaluation of new thiazolo[5,4-d]pyrimidine derivatives as potent antiproliferative agents.
August 2017, MedChemComm,
Copied contents to your clipboard!