Supplementary Materialsmolecules-22-00561-s001. in stem cell element (SCF) release by treated tumor cells. Although less cytotoxic, the free ligand inhibits the surface marker CD133 expression in hepatocarcinoma cells, and in HT-29 colon carcinoma. The new synthesized Pd(II) complexes 1 and 2 exhibit an important potential through their selective cytotoxic activity and by targeting the stem-like tumor cell populations, which leads to the tumor growth arrest and prevention of metastasis. rhizome, has a wide usage in medicine, food YM90K hydrochloride industry and cosmetics, based on its beneficial properties. This biologically active component proved antioxidant, anti-inflammatory, antitumor activities and it was found to be useful in many chronic diseases, including cancer [7,8]. The attempt to bring curcumin into antitumor chemotherapy protocols together with standard drugs led to the reduction of colon stem-like cancer cells in vitro . Although, curcumin and its analogues manifest a noticeable biological activity, they exhibit poor bioavailability because of low absorption, rapid metabolism, and rapid systemic elimination , having a limited solubility in water and other solvents. Several curcumin analogues including 1,7-bis(2-methoxyphenyl)hepta-1,6-diene-3,5-dione, displayed antioxidant activity , suppression of the NF-B expression through the tumor necrosis factor- pathway  and anti-inflammatory activity [13,14]. Derivatives of curcumin with appropriate substituents in the 4th position played an important role within the chemoprevention and chemotherapy of glioma and pores and skin cancer . Furthermore, halogenated curcumin analogues to be able to bind supplement D receptor, may low the chance of digestive tract and epithelial tumor . Alternatively, in tumor chemotherapy protocols the metal-based medicines have gained a significant role, consequently curcumin and its own metallic complexes had been researched for his or her restorative properties intensely, like the gastrointestinal malignancies [8,17]. Although, the oxaliplatin medication can be by way of a choice in colorectal tumor treatment  right now, lately palladium also was thoroughly examined, by means of coordinative substances with YM90K hydrochloride energetic ligands biologically, in vitro, in cancer of the colon [19,20,21]. Although platinum and palladium complexes are found in the tumor therapy  frequently, those including curcumin or curcumins analogues became effective as antitumor real estate agents [23 also,24,25,26,27]. In previous studies, the verification was got by us of effectiveness of metallic complexes of curcumin regarding the antineoplastic activity in ovarian, colorectal, melanoma, cervical, breasts and liver organ carcinomas [28,29,30], an undeniable fact that prompted us to help expand investigations of such coordination versions. Curcumin acts against cancer stem cells by interferences YM90K hydrochloride with several Rabbit Polyclonal to CD3EAP signaling pathways , and the coordination of curcumin and its analogues to metals may increase the selectivity for biological targets and improve their bioavailability levels in tumor cells . Herein, the synthesis, characterization and biological application as antitumor biomaterials YM90K hydrochloride of Pd(II) complexes with 1,7-bis(2-methoxyphenyl)hepta-1,6-diene-3,5-dione are described. The new palladium(II) complexes (1 and 2) growth inhibition was assessed in vitro on human colorectal (HT-29 and DLD-1) cell populations and hepatic CSC stem-like tumor cells derived from a hepatic metastasis. To emphasize their selectivity, identical assessments were made on normal liver cells (LIV) and on normal progenitor hematopoietic blood cells. The mechanism of action of complexes 1, 2 and of curcumin-like ligand was elucidated tracking an important stem cell marker: the prominin-1 or CD133 expression of the treated cells membrane. Moreover, Stem Cell Factor (SCF) release was also measured in vitro. The biologic outcome of the novel complexes indicates that they are better prodrugs as the free ligand, and proved the Pd(II) complexes capacity to target the cancer stem-like cells which sustain the tumor growth. 2. Results and Discussion 2.1. Synthesis and Characterization Two palladium(II) complexes with 1,7-bis(2-methoxyphenyl)hepta-1,6-diene-3,5-dione were synthesized and structurally characterized. Coordination of the free ligand with palladium was meant for improving the compounds bioavailability and toxicity by increasing its selectivity and targeting the tumor cells. Novel Pd(II) complexes 1 and 2, were obtained by reacting the precursor palladium complexes [(C10H22N2)Pd(OAc)2] and [(C6H14N2)Pd(OAc)2] with the curcumin analogue, 1,7-bis(2-methoxyphenyl)hepta-1,6-diene-3,5-dione in an equimolecular ratio (Scheme 1). All complexes, including also the precursors have been characterized by 1H- and 13C-NMR spectroscopy, IR spectroscopy, mass spectrometry, the analytical data becoming presented in the techniques and Components and Supplementary Materials sections. 2.2. Cytotoxicity Assessments In vitro, the Pd(II)complexes.