Synthesis and activity mechanism of some novel 2-substituted benzothiazoles as hGSTP1-1 enzyme inhibitors.

Human GSTP1-1 is one of the most important proteins, which overexpresses in a large number of human tumours and is involved in the development of resistance to several anticancer drugs. So, it has become an important target in cancer treatment. In this study, 12 benzothiazole derivatives were synthesized and screened for their in vitro inhibitory activity for hGSTP1-1. Among these compounds, two of them (compounds #2 and #5) have been found to be the leads when compared with the reference drug etoposide. In order to analyse the structure-activity relationships (SARs) and to investigate the binding side interactions of the observed lead compounds, a HipHop pharmacophore model was generated and the molecular docking studies were performed by using CDocker method. In conclusion, it is observed that the lead compounds #2 and #5 possessed inhibitory activity on the hGSTP1-1 by binding to the H-site as a substrate in which the para position of the phenyl ring of the benzamide moiety on the benzothiazole ring is important. Substitution at this position with a hydrophobic group that reduces the electron density at the phenyl ring is required for the interaction with the H side active residue Tyr108.

Subtrochanteric valgus-extension osteotomy for neglected congenital dislocation of the hip in young adults.

Thirty-five patients with unilateral or bilateral neglected congenital dislocation of the hip (CDH) were treated with subtrochanteric valgus-extension osteotomy between 1975 and 1992. There were 29 females and 6 males in the group. A total of 50 osteotomies was performed. The mean age of the patients was 22 years; the mean follow-up was 7 years. Before operation, the main complaints were pain and gait abnormalities. Leg-length discrepancy was another problem, especially for unilateral cases. The main indication for the operation was pain. This pelvic support osteotomy was performed to correct the instability of the hip and as a result of this to relieve pain. Patients were retrospectively evaluated based upon Harris Hip Score and self-evaluation. The mean Harris Hip Score was 49 before operation and improved to 72 after the operation. Alleviation of the pain was the most significant functional outcome of the treatment. It was also noted that limping could be improved if an adequate rehabilitation program was followed. We conclude that in neglected CDH cases with pain, limping and lumbar hyperlordosis in the young adult, a subtrochanteric valgus-extension osteotomy can give satisfactory results.

Skin blood flow level and stump healing in ischemic amputations.

Skin blood flow was measured with xenon 133-histamine mixture in 20 lower extremities of 18 patients before performing amputations. The amputation levels were chosen according to clinical criteria; 13 below-knee, 3 distal femoral, 1 midfemoral, 2 transmetatarsal, and 1 Syme's amputations were performed. Fourteen stumps had normal healing, 2 had delayed healing, and 3 had necrosis. All of the stumps with normal healing had a skin blood flow >1.76 ml/100 g tissue/minute. Bleeding from the skin also was a good predictor of healing. Skin blood flow measurement may be helpful for level selection in ischemic amputations.