Gold(i) complexes with anticancer properties and methods of use thereof

Abstract

Monomeric and dimeric gold(I) complexes as anticancer agents. The gold(I) complexes are coordinated to mixed ligands: one phosphine-based ligand that may be monodentate or bidentate and at least one dithiocarbamate-based ligand that is monodentate. Pharmaceutical compositions incorporating the gold(I) complexes, methods of synthesis, methods of treating cancer and methods of inhibiting cancer cell proliferation and inducing cancer cell apoptosis are also provided.

1 : A composition comprising:
 a gold(I) complex having Formula 3, or a pharmaceutically acceptable salt or ester thereof,   at least one protein kinase inhibitor, and   a hydrophobic carrier,   wherein Formula 3 is:   
       
         
           
           
               
               
           
         
       
     
     
         2 - 5 : (canceled) 
     
     
         6 : The composition of  claim 1 , wherein the composition is in a solid, semi-solid, or liquid dosage form. 
     
     
         7 : The composition of  claim 1 , wherein the composition is formulated for one or more modes of administration selected from the group consisting of oral administration, systemic administration, parenteral administration, inhalation spray, infusion, rectal administration, topical administration, intravesical administration, intradermal administration, transdermal administration, subcutaneous administration, intramuscular administration, intralesional administration, intracranial administration, intrapulmonal administration, intracardial administration, infrasternal administration and sublingual administration. 
     
     
         8 : A method for inhibiting proliferation of cancer cells, comprising:
 contacting the cancer cells with the composition of  claim 1 .   
     
     
         9 : The method of  claim 8 , wherein the cancer cells are human cells. 
     
     
         10 : The method of  claim 8 , wherein the cancer cells are at least one selected from the group consisting of lung cancer cells, colorectal cancer cells and cervical cancer cells. 
     
     
         11 : The method of  claim 8 , wherein the gold(I) complex concentration is 5-50 μM. 
     
     
         12 : The method of  claim 8 , wherein the gold(I) complex exhibits an IC 50  of 1-150 μM for inhibiting the proliferation and inducing the apoptosis of the cancer cells. 
     
     
         13 : The composition of  claim 1 , further comprising at least one chemotherapeutic agent selected from the group consisting of aflibercept, asparaginase, bleomycin, busulfan, carmustine, chlorambucil, cladribine, cyclophosphamide, cytarabine, dacarbazine, daunorubicin, doxorubicin, etoposide, fludarabine, gemcitabine, hydroxyurea, idarubicin, ifosfamide, irinotecan, lomustine, mechlorethamine, melphalan, mercaptopurine, methotrexate, mitomycin, mitoxantrone, pentostatin, procarbazine, 6-thioguanine, topotecan, vinblastine, vincristine, retinoic acid, oxaliplatin, carboplatin, 5-fluorouracil, teniposide, amasacrine, docetaxel, paclitaxel, vinorelbine, bortezomib, clofarabine, capecitabine, actinomycin D, epirubicin, vindesine, methotrexate, and tipifarnib. 
     
     
         14 : The composition of  claim 1 , further comprising at least one antineoplastic antibody selected from the group consisting of trastuzumab, cetuximab, panitumumab, rituximab, bevacizumab, mapatumumab, conatumumab, and lexatumumab. 
     
     
         15 : The composition of  claim 1 , wherein the at least one protein kinase inhibitor treats at least one cancer selected from the group consisting of lung cancer, colorectal cancer, and cervical cancer. 
     
     
         16 : The composition of  claim 1 , wherein the at least one protein kinase inhibitor is selected from the group consisting of imatinib, erlotinib, sorafenib, sunitinib, dasatinib, nilotinib, lapatinib, gefitinib, temsirolimus, everolimus, rapamycine, bosutinib, pzopanib, axitinib, neratinib, vatalanib, pazopanib, midostaurin, and enzastaurin. 
     
     
         17 : The composition of  claim 15 , wherein the at least one protein kinase inhibitor treats lung cancer. 
     
     
         18 : The composition of  claim 16 , wherein the at least one protein kinase inhibitor is erlotinib, gefitinib, or both. 
     
     
         19 : The composition of  claim 1 , wherein the hydrophobic carrier is a vegetable oil, a vegetable fat, or both. 
     
     
         20 : The composition of  claim 19 , wherein the vegetable oil is at least one selected from the group consisting of corn oil, cottonseed oil, peanut oil, and sesame oil. 
     
     
         21 : The composition of  claim 19 , wherein the vegetable fat is cocoa butter. 
     
     
         22 : The composition of  claim 1 , which consists essentially of the gold(I) complex, the protein kinase inhibitor, and the hydrophobic carrier. 
     
     
         23 : The composition of  claim 1 , which consists of the gold(I) complex, the protein kinase inhibitor, and the hydrophobic carrier.