Search

Based on a new semisynthetic route, a series of phosphotriester 7-alkyl-homocamptothecin derivatives are designed and synthesized. Cytotoxic activity assays show that compounds 12a and 14c with a methyl in position C7 of the homocamptothecin are more potent than the other derivatives and the positive drug irinotecan against A-549, MCF-7, and LOVO cell lines. Moreover, compound 14c shows potent tumour inhibitory activity in a Colo205 xenograft model. [ABSTRACT FROM AUTHOR]

Abstract: The SN2 reaction of enantiomerically pure sulfonates with the tunable complex of R3N–R′COOH in toluene has been extensively studied. It was revealed that the molar ratio of the tertiary amines and carboxylic acids in the complex of R3NR′COOH is crucial for the SN2 reaction, and should be tuned for each sulfonate to give the best yield. Fifteen sulfonates 1 and 3–13 (Scheme 2) were prepared and transformed into 22 corresponding inverted esters 2 and 14–24 (Scheme 2) in good to high yields. [Copyright &y& Elsevier]

Objective: To evaluate the safety, effectiveness, and outcomes of holmium laser enucleation of the prostate (HoLEP) for patients with symptomatic enlarged prostate after 11 years of experience., Methods: The 3162 evaluable patients treated with holmium laser enucleation of the prostate at our institution between August 2001 and August 2011 were retrospectively analyzed. Study variables included International Prostate Symptom Score, quality of life, maximum urinary flow rate, and incidence of complications., Results: HoLEP were performed successfully completed, not patients which occurs as electric cutting syndrome. The operation time was (60.8 ± 18.4) minutes; average resection of prostate quality was (45.4 ± 24.4) g. The hemoglobin reduce though surgery was (1.81 ± 0.93) g/L; percentage of red blood cell change was 1.24% ± 0.43%, and sodium blood drop was (1.14 ± 0.35) mmol/L. Postoperative patients of hospital stay (3.1 ± 1.1) days, average time of indwelling catheter time was (2.3 ± 0.8) days. Patients were followed up for 6-131 months time, an average of 32.4 months. Postoperative patients with international prostate symptom score progressive declined. The quality of life score was 2.2 ± 1.7, and it less than preoperative (5.7 ± 3.3, t = 2.447, P < 0.01). The time of follow-up droped further, and postoperative comparative differences have statistical significance (t = 2.179, 2.228, 2.306 and 2.365, P < 0.05). The maximum urinary flow rate also improved (P < 0.05). Postoperative complications included bladder neck contracture (4 cases), urinary tract infection (107 cases), urethral stricture (11 cases) and urinary incontinence (11 cases). The 11 patients reoperation., Conclusions: HoLEP treatment of benign prostatic hyperplasia could achieve the advantages of open surgery the same effect. It had fewer damage, faster recovery, fewer complications, and is a good treatment option.

Photodynamic therapy (PDT) is a promising cancer treatment modality that uses dye-sensitized photooxidation of biologic matter in target tissue. This study explored effects of the photosensitizer BCPD-17 during PDT for osteosarcoma. LM-8 osteosarcoma cells were treated with BCPD-17 and cell viability after laser irradiation was assessed in vitro with the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. The effects of BCPD-17 during PDT recurrence were then examined on tumor-bearing mice in vivo. BCPD-17 had dose- dependent cytotoxic effects on LM-8 osteosarcoma cells after laser irradiation which also had energy-dependent effects on the cells. The rate of local recurrence was reduced when marginal resection of mice tumors was followed by BCPD-17-mediated PDT. Our results indicated BCPD-17-mediated PDT in combination with marginal resection of tumors is a potentially new effective treatment for osteosarcoma.

To clarify the important functional residues in the active site of N-myristoyltransferase (NMT), a novel antifungal drug target, and to guide the design of specific inhibitors, multiple sequence alignments were performed on the NMT family and thus evolutionary trace was constructed. The important functional residues in myristoyl CoA binding site, catalytic center and inhibitor binding site of NMT family were identified by ET analysis. The trace residues were mapped onto the active site of CaNMT. Trpl26, Asn175 and Thr211 are highly conserved trace residues and do not interact with current NMT inhibitors, which are potential novel drug binding sites for the novel inhibitor design. Pro338, Leu350, Ile352 and Ala353 are class-specific trace residues, which are important for the optimization of current NMT inhibitors. The trace residues identified by ET analysis are of great importance to study the structure-function relationship and also to guide the design of specific inhibitors.

Aim: A series of triazole antifungal agents were synthesized to search for novel triazole antifungal agents with more potent activity, less toxicity and broader spectrum., Methods: Twenty-one 1-(1H-1, 2, 4-triazolyl)-2-(2, 4-diflurophenyl)-3-(4-substituted-1-piperazinyl)-2-propanols were synthesized, on the basis of the three dimensional structure of P450 cytochrome 14alpha-sterol demethylase (CYP51) and their antifungal activities were also evaluated., Results: Results of preliminary biological tests showed that most of title compounds exhibited activity against the eight common pathogenic fungi to some extent and the activities against deep fungi were higher than that against shallow fungi. In general, phenyl and pyridinyl analogues showed higher antifungal activity than that of the phenylacyl analogues., Conclusion: Several title compounds showed higher antifungal activities than fluconazole and terbinafine. Compound VIII-1, 4, 5 and IX-3 showed the best antifungal activity with broad antifungal spectrum and were chosen for further study.