Anti-inflammation and antimalarial profile of 5-pyridin-2-yl-1H-[1,2,4]triazole-3-carboxylic acid ethyl ester as a low molecular intermediate for hybrid drug synthesis

A novel 1,2,4-triazole intermediate 5-pyridin-2-yl-1H-[1,2,4]triazole-3-carboxylic acid ethyl ester was prepared by the reaction of N’-aminopiridyne-2-carboximidamine and an excess monoethyl oxalyl chloride and screened for biological activities. The compound was structurally characterized by nuclear magnetic resonance spectroscopy, elemental analysis, infrared spectroscopy, and single-crystal X-ray diffraction. Bioassays indicated that the compound exhibits potent anti-inflammation activity in vitro. An egg albumin denaturation assay to assess the anti-inflammatory effect of the synthesized compound showed a significant inhibition of protein with a maximum inhibition of 71.1% at the highest tested concentration (1000 µg/mL) compared to 81.3% for Aspirin as standard drug. The antimalarial activity on the 3D7 P. falciparum strain was determined to be IC50 176 µM and was obtained prior to connection with pharmacophoric groups

Bone formation at recombinant human bone morphogenetic protein-2-coated titanium implants in the posterior mandible (Type II bone) in dogs

BACKGROUND: Conventional oral/maxillofacial implants reach osseointegration over several months during which the titanium fixtures interact with alveolar bone. The objective of this study was to determine if adsorbing recombinant human bone morphogenetic protein-2 (rhBMP-2) onto a titanium porous oxide (TPO) implant surface might enhance or accelerate local bone formation and support osseointegration in a large animal oral/maxillofacial orthotopic model. MATERIAL AND METHODS: Endosseous implants with a TPO surface were installed into the edentulated posterior mandible in eight adult Hound Labrador mongrel dogs. The implant surface had been adsorbed with rhBMP-2 at 0.2 or 4.0 mg/ml. TPO implants without rhBMP-2 served as control. Treatments were randomized between jaw quadrants. Mucosal flaps were advanced and sutured leaving the implants submerged. Clinical and radiographic evaluations were made immediately post-surgery, at day 10 (suture removal), and week 4 and 8 post-surgery. The animals received fluorescent bone markers at week 3, 4, and at week 8 post-surgery, when they were euthanized for histologic analysis. RESULTS: TPO implants coated with rhBMP-2 exhibited dose-dependent bone remodelling including immediate resorption and formation of implant adjacent bone, and early establishment of clinically relevant osseointegration. The resulting bone-implant contact, although clinically respectable, appeared significantly lower for rhBMP-2-coated implants compared with the control [rhBMP-2 (0.2 mg/ml) 43.3+/-10.8%versus 71.7+/-7.8%, p<0.02; rhBMP-2 (4.0 mg/ml) 35.4+/-10.6%versus 68.2+/-11.0%, p<0.03]. CONCLUSIONS: rhBMP-2 adsorbed onto TPO implant surfaces initiates dose-dependent peri-implant bone re-modelling resulting in the formation of normal, physiologic bone and clinically relevant osseointegration within 8 weeks.This study was supported by a grant from Wyeth Research, Cambridge, MA, USA, and Nobel Biocare AB, Go¨teborg, Sweden. Jan Hall is an employee of Nobel Biocare AB. Rachel G. Sorensen was an employee of Wyeth Research at the time of study. John Wozney is an employee of Wyeth Research. Ulf M. E. Wikesjo¨ was an employee of Wyeth Research, and presently serves as consultant to Wyeth Research and Nobel Biocare AB

Bone-implant contact at calcium phosphate-coated and porous titanium oxide (TiUnite (TM))-modified oral implants

Background: Calcium phosphate (CP)-coated implants are usually referred to as having osteoconductive properties, whereas titanium implants with a native oxide layer are considered less osteoconductive. Often smooth titanium oxides (TOs) are compared to relatively rough CP structures. The objective of this study was to evaluate osteoconduction by comparing bone–implant contact at a relatively smooth, highly crystalline CP coating with a structured, porous TO (TiUnitet)-modified surface. Material and methods: Ten adult Hound Labrador mongrel dogs were used. Four titanium implants (Nobel Biocare) with CP-coated (2) or TO-modified (2) surfaces were installed 12 weeks following mandibular premolar and molar teeth extraction. The implants were alternated within and between jaw quadrants in consecutive animals. Mucosal flaps were advanced and sutured leaving the implants in a submerged position. The animals were injected with fluorescent bone labels at 3 and 4 weeks postsurgery, and pre-euthanasia to monitor progress of bone formation. The animals were euthanized at 8 weeks postsurgery and block biopsies were prepared for histologic and histometric analysis. Results: There were no remarkable differences in bone formation and apparent bone– implant contact comparing the TO-modified and CP-coated surfaces. However, the measured average bone–implant contact was 71% and 57% (P¼0.027) for TO-modified and CP-coated implants, respectively. Conclusions: We conclude that the TO surface exhibits osteoconductive properties exceeding that of the CP surface. One or several of the chemical and physical properties of the TO surface may result in the remarkable bone formation along its surface. This study indicated that crystallinity and/or chemistry may be important