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A Preliminary Study on Combination Therapy of Artemisinin Dimer Oxime and Topotecan against Nonsmall Cell Lung Cancer in Mice

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World Journal of Traditional Chinese Medicine 2018年第1期4卷 8-14页

作者： Mohammad K.Ashfaq Mohamed Sadek Abdel-Bakky Mir Tahir Maqbool Waseem Gul mahmoud A.elsohly National Center for Natural Product Research School of Pharmacy University of Mississippi University Faculty of Pharmacy Al-Azhar University elsohly Laboratory Incorporation Industrial Drive Oxford Department of Pharmaceutics School of PharmacyUniversity of Mississippi University

Background: Artemisinin dimer oxime – dimer molecule synthesized from artemisinin possesses high bioavailability and marked in vitro anticancer activities against solid tumor?derived cell lines, endothelial cell proliferation, migration, and angiogenic processes. Numerous murine models have been developed to study human cancer. The most widely used models are the human tumor xenograft mouse model. Materials and Methods: In this study, human tumor cells(NCI?H640, 1 × 107 in 100 μL) are implanted subcutaneously, or 1 × 107 in 50 μL in the thoracic cavity, in athymic nude mice(nu/nu). The implanted cells were allowed to grow for 10 days before initiation of drug treatment(dimer oxime and topotecan, ip). Tumor volume and thoracic/body weight ratio were recorded. Results: We successfully established subcutaneous and thoracic xenografts with human nonsmall cell lung cancer cell line xenografts in athymic nude mice in only 10 days. Using these models, we attempted treatment of xenografts with topotecan – a known anticancer drug and artemisinin dimer oxime or combination of these two drugs. Combination therapy showed a significant reduction in tumor volume and tumor/body weight. Treatments with combination of topotecan and dimer oxime resulted in the reduced mortality rates in comparison with untreated mice. Conclusions: Xenograft tumor models are useful for preclinical screening of new pharmacophores. From this preliminary study, it appears that combination of dimer oxime and topotecan may be used as chemotherapeutic agents against nonsmall cell lung cancer. Further studies are needed to evaluate other combination treatment regimens as well as the mechanism(s) of action.

关键词： Artemisinin cancer dimer oxime topotecan xenografts

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Expanding the Therapeutic Spectrum of Artemisinin:Activity Against Infectious Diseases Beyond Malaria and Novel Pharmaceutical Developments

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World Journal of Traditional Chinese Medicine 2016年第2期2卷 1-23页

作者： Thomas Efferth Marta R.Romero Anna Rita Bilia Ahmed Galal Osman mahmoud elsohly Michael Wink Rudolf Bauer Ikhlas Khan Maria Camilla Bergonzi Jose J.G.Marin Department of Pharmaceutical Biology Institute of Pharmacy and Biochemistry Johannes Gutenberg University Experimental Hepatology and Drug Targeting (HEVEFARM) CIBERehd IBSAL University of SalamancaCampus Miguel de Unamuno Department of Chemistry "Ugo Schiff" University of Florence National Center for Natural Products Research School of Pharmacy University of Mississippi elsohly Laboratories Inc. Department of Pharmaceutics University of Mississippi Institute of Pharmacy and Molecular Biotechnology Ruprecht-Karls University Institute of Pharmaceutical Sciences Department of Pharmacognosy University of Graz Devision of Pharmacognosy Department of Biomolecular Sciences University of Mississippi

The interest of Western medicine in Traditional Chinese Medicine(TCM) as a source of drug leads/new drugs to treat diseases without available efficient therapies has been dramatically augmented in the last decades by the extensive work and the outstanding findings achieved within this kind of medicine. The practice of TCM over thousands of years has equipped scientists with substantial experience with hundreds of plants that led to the discovery of artemisinin(qinghaosu), which is extracted from the medicinal plant Artemisia annua L.(qinghao). The unexpected success of artemisinin in combating malaria has drawn strong attention from the scientific community towards TCM. Artemisinin was discovered by Youyou Tu in 1972. Since then, several novel pharmacological activities based on the well-known properties of the sesquiterpene lactone structure with the oxepane ring and an endoperoxide bridge have been unravelled. Beyond malaria, artemisinin and its derivatives(artemisinins) exert profound activities towards other protozoans(Leishmania, Trypanosoma, amoebas, Neospora caninum, and Eimeria tenella), trematodes(Schistosoma, liver flukes), and viruses(human cytomegalovirus, hepatitis B and C viruses). Less clear is the effect against bacteria and fungi. Based on the promising results of artemisinin and the first generation derivatives(artesunate, artemether, arteether), novel drug development strategies have been *** included the synthesis of acetal-and non-acetal-type artemisinin dimeric molecules as well as developing nanotechnological approaches, ***-based liposomes, niosomes, micelles, solid lipid nanocarriers, nanostructured lipid carriers, nanoparticles, fullerenes and nanotubes. The current review presents an overview on different aspects of artemisinins, including sources, chemistry, biological/pharmacological properties, types of infectious pathogens that are susceptible to artemisinins in vitro and in vivo, in addition to the advancement in

关键词： Artemisinin derivatives Artemisia annua Asteraceae Antimalarial drugs Anti-pathogen activity Antiviral properties Artemisinin-loaded nanocarriers Traditional Chinese Medicine

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