title: Synthesis of a series of novel dihydroartemisinin monomers and dimers containing chalcone as a linker and their anticancer activity.
abstract: A new series of monomer and dimer derivatives of dihydroartemisinin (DHA) containing substituted chalcones as a linker were synthesized and investigated for their cytotoxicity in human cancer cell lines HL-60 (leukemia), Mia PaCa-2 (pancreatic cancer), PC-3 (prostate cancer), LS180 (colon cancer) and HEPG2 (hepatocellular carcinoma). Some of these derivatives have greater antiproliferative and cytotoxic effects in tested cell lines than parent compound DHA. The structures of the all compounds were confirmed by IR, (1)H NMR and mass spectral data. Among the new derivatives, compounds 8, 14, 15, 20 and 24 were found to be more active than parent DHA against tested human cancer cell lines. DHA derivatives were found to be most active in human leukemia cell lines with compounds 8, 14, 15, 20 and 24 showed IC50 values less than 1 μM for 48 h whereas DHA has IC50 value of 2 μM at same time period. The most potent compounds 8 with IC50 = 0.3 μM (at par with doxorubicin (IC50 = 0.3 μM)) and 15 with IC50 = 0.4 μM, of the series, six and three times active than DHA (with IC50 = 2 μM) respectively were selected for further mechanistic work in human leukemia HL-60 cells.
authors.affiliation: Medicinal Chemistry Department, Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110001, India.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Gaur
authors.affiliation: Department of Cancer Pharmacology, Indian Institute of Integrative Medicine, Canal Road Jammu, Jammu and Kashmir, 180001, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110001, India.
authors.forename: Anup Singh
authors.initials: AS
authors.lastname: Pathania
authors.affiliation: Department of Cancer Pharmacology, Indian Institute of Integrative Medicine, Canal Road Jammu, Jammu and Kashmir, 180001, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110001, India. Electronic address: fmalik@iiim.ac.in.
authors.forename: Fayaz Ahmad
authors.initials: FA
authors.lastname: Malik
authors.affiliation: Medicinal Chemistry Department, Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110001, India. Electronic address: bhakunirs2000@gmail.com.
authors.forename: Rajendra Singh
authors.initials: RS
authors.lastname: Bhakuni
authors.affiliation: Medicinal Chemistry Department, Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, India.
authors.forename: Ram Kishor
authors.initials: RK
authors.lastname: Verma
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D037621:Artemisinins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002599:Chalcone / Q000737:chemistry*; D060326:Chemistry Techniques, Synthetic; D019281:Dimerization; D015195:Drug Design; D018922:HL-60 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D037621:Artemisinins; D002599:Chalcone; C039060:artenimol
keywords: Apoptosis; Artemisinin; Leukemia; Monomer and dimer; Synthesis