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Dactylolide and certain analogues are attractive targets for study due to their structural resemblance to zampanolide, a very promising anticancer lead compound and a unique covalent-binding microtubule stabilizing agent. The primary goal of this project is identification and synthesis of simplified analogues of dactylolide that would be easier to prepare and could be investigated for antiproliferative activity in comparison with zampanolide. Extension of Almann’s concept of a simplified zampanolide analogue to dactylolide in the form of desTHPdactylolide was attractive not only for reasons of synthetic simplification but also for the prospect that analogues of dactylolide could be prepared in both (17 S ) and (17 R ) configurations. Since Altmann’s overall yield for the six-step procedure leading to the C9–C18 fragment of desTHPdactylolide was only 8.7%, a study focused on optimized synthesis and antiproliferative evaluation of each enantiomer of desTHPdactylolide was initiated using Altmann’s route as a framework. To this end, two optimized approaches to this fragment C9–C18 were successfully developed by us using allyl iodide or allyl tosylate as the starting material for a critical Williamson ether synthesis. Both (17 S ) and (17 R ) desTHPdactylolides were readily synthesized in our laboratory using optimized methods in yields of 37–43%. Antiproliferative activity of the pair of enantiomeric desTHPdactylolides, together with their analogues, was evaluated in three docetaxel-sensitive and two docetaxel-resistant prostate cancer cell models using a WST-1 cell proliferation assay. Surprisingly, (17 R ) desTHPdactylolide was identified as the eutomer in the prostate cancer cell models. It was found that (17 S ) and (17 R ) desTHPdactylolide exhibit equivalent antiproliferative potency towards both docetaxel-sensitive (PC-3 and DU145) and docetaxel-resistant prostate cancer cell lines (PC-3/DTX and DU145/DTX). [ABSTRACT FROM AUTHOR]

• Prostate cancer cells show different radiosensitivity than reference cells. • Radiosensitivity differences affect the final clinical dose distribution. • Prostate cancer cell-based clinical dose from one-directional irradiation is no longer flat. • Opposed left–right irradiation used in clinic improves this lack of flatness. [Purpose] Treatment plans for carbon ion radiotherapy (CIRT) in Japan are designed to uniformly deliver the prescribed clinical dose based on the radiosensitivity of human salivary gland (HSG) cells to the planning target volume (PTV). However, sensitivity to carbon beams varies between cell lines, that is, it should be checked that the clinical dose distribution based on the cell radiosensitivity of the treatment site is uniform within the PTV. [Methods] We modeled the linear energy transfer (LET) dependence of the linear-quadratic (LQ) coefficients specific to prostate cancer, which accounts for the majority of CIRT. This was achieved by irradiating prostate cancer cells (PC3) with X-rays from a 4 MV-Linac and carbon beams with different LETs of 11.1–214.3 keV/μm. By using the radiosensitivity of PC3 cells derived from cellular experiments, we reconstructed prostate-cancer-specific clinical dose distributions on patient computed tomography (CT). [Results] The LQ coefficient, α, of PC3 cells was larger than that of HSG cells at low (<50 keV/μm) LET and smaller at high (>50 keV/μm) LET, which was validated by cellular experiments performed on rectangular SOBPs. The reconstructed dose distribution on patient CT was sloped when 1 fraction incident from the one side of the patient was considered, but remained uniform from the sum of 12 fractions of the left–right opposing beams (as is used in clinical practice). [Conclusion] Our study reveals the inhomogeneity of clinical doses in single-field plans calculated using the PC3 radiosensitivity data. However, this inhomogeneity is compensated by using the combination of left–right opposing beams. [ABSTRACT FROM AUTHOR]

In this study, novel silicon phthalocyanines complexes have been synthesized, characterized and compared their antitumor efficiency of photodynamic, sonodynamic, sonophotodynamic on prostate cancer cells. Sonophotodynamic therapy (SPDT), a combination of photodynamic therapy (PDT) and sonodynamic therapy (SDT), is a new and promising method for the treatment of cancer cells. Although it is known that SPDT therapy has improved potential therapeutic result, the development of this method by working with different sensitizers has been lacking in the literature. To the best of our knowledge, this paper is the first study in the literature to calculate the photochemical properties of synthesized molecules and compare the results of photodynamic, sonodynamic and sonophotodynamic therapies on prostate cancer cells. In this study, new water soluble sensitizers with the different properties of linker heteroatom (O or S) were synthesized, characterized and analyzed their photophysicochemical properties. Then, the effects of sonodynamic, photodynamic and sonophotodynamic on these sensitizers were examined in vitro on prostate cancer using PC3 cells. For this purpose, the cells were incubated with various concentrations of chemicals and subjected to ultrasound and/or light irradiation. According to MTT results, the sensitizers were showed quite efficiency for sonodynamic, photodynamic and sonophotodynamic therapies and decreased cell viability when compared with control group. Also apoptosis measurement data shows that the sensitizers (1a , 1b) would produce much better effects by combination sonodynamic and photodynamic therapies, especially the measurement of apoptotic cells in complex 2a reached 95% after SPDT therapy. As a result, it is seen that SPDT is a combination which has enhanced the therapeutic outcome. Image 1 • The novel water soluble silicon (VI) phthalocyanines bearing quinolone moieties. • The photochemical and photophysical properties of these phthalocyanines were investigated. • Compared their antitumor efficiency of photodynamic, sonodynamic and sonophotodynamic on prostate cancer cells. • Apoptotic cell were observed in 95% in SPDT studies for 2a. [ABSTRACT FROM AUTHOR]