Efficient microwave synthesis of flurbiprofen derivatives and their enhancement of efficacy in chronic inflammatory pain models and gastro-protective potential in post-operative model.

Present research was designed to synthesize and characterize the flurbiprofen derivatives and to evaluate their analgesic, anti-inflammatory and gastro-protective activities in post-operative and chronic inflammatory pain models. Flurbiprofen derivatives were produced by using three-step processes involving esterification, hydrazide production, and schiff base, each of which modified a different carboxyl group. All the newly synthesized flurbiprofen derivatives (NS5-NS8) were characterized by 1H NMR,13C NMR,19F NMR and HR-ESI-MS, and the post-operative, inflammatory pain and ulcerogenic activities were determined in well-established in-vivo animal models. To evaluate post-operative and inflammatory pain, various doses of compounds [1, 3, 10, and 30 mg/kg (bwt)] were used, while their ulcerogenic potential was assessed at doses of 100 and 150 mg/kg (bwt). The incisional damage linked pain was significantly (p < 0.001) reduced by derivatives at different doses in both the acute and repeated tests with decreased response of phologistic agent-induced inflammation. The stomach histology and biochemical features demonstrate that the synthesized derivatives have no potential to cause ulcerogenicity as compared to aspirin and flurbiprofen. Furthermore, docking shows that the hydrazide moiety of these compounds is crucial in interacting within COX-2 binding site. Therefore, the synthesized compounds exhibit strong analgesic and anti-inflammatory effects and a low risk of causing ulcers. These attributes render them potentially valuable therapeutic agents for the treatment of pathological disorders associated with inflammation and pain.Communicated by Ramaswamy H. Sarma.

Primary amenorrhea in females attending gynaecological outpatient of a tertiary care hospital at Peshawar.

OBJECTIVE: To determine the aetiological factors of amenorrhea. METHODS: The pilot cross-sectional study was conducted in Government Naserullah Khan Babar Memorial Hospital, Peshawar, Pakistan, from January 2015 to December 2017, and comprised amenorrhea cases. Cases were analysed according to their clinical profile, ultrasound findings and biochemical tests. Data was analysed using SPSS 20. RESULTS: There were 100 patients with a mean age of 22.17±5.52 years (range: 14-36 years). Anatomical defects were the most common cause in 60(60%) patients. Imperforate hymen and transverse vaginal septum were found in 7(7%), 7(7%) patients each, while mullerian abnormalities were found in 46(46%) patients. Hypergonadotropic hypogonadism and polycystic ovarian syndrome were found in 17(17%) patients each. CONCLUSIONS: Anatomical defects were found to be the most common cause among amenorrhea patients.

Chemotherapeutic Potential of Carthamus Oxycantha Root Extract as Antidiarrheal and In Vitro Antibacterial Activities.

Our research work was designed to investigate the curative and preventive effects of Carthamus oxycantha root extract against diarrhea and microorganisms. For the antibacterial experiment, the agar well diffusion method was used against standard bacteria Staphylococcus aureus, Escherichia coli, Pseudomonas aeroginosa, and Salmonella typhi, while for the assessment of antidiarrheal activity, castor oil and the magnesium sulfate-induced diarrhea method was used on albino, laboratory-bred (BALB/c) mice at a dose rate of 200 and 400 mg/kg (body weight, b.w) orally. The methanol extract of C. oxycantha significantly (p < 0.001) decreased the frequency of defecation, and wet stools in a dose depended on the manner of after receiving magnesium sulfate (2 g/kg (b.w)) and castor oil (1.0 mL/mice). Furthermore, the extract of C. oxycantha showed concentration-dependent antimicrobial properties against S. aureus followed by S. typhi, E. coli, and P. aeroginosa bacterial strains, with inhibitions ranging from 10.5-15 mm. These findings show significant results that C. oxycantha is effective as an antidiarrheal and antibacterial agent. However, further works are needed to establish its mode of action.

Steroidal alkaloids efficient aromatase inhibitors with potential for the treatment of postmenopausal breast cancer.

Plant-derived natural products are of great interest due to their diversity in modern drug discovery. Sarcococca saligna has been used for the treatment of different diseases. The present study was aimed at isolating phytochemical constituents including Alkaloid-C (a), Dictyophlebine (b), Sarcovagine-D (c) and Saracodine (d) Holaphylline (e) from Sarcococca saligna to investigate the anticancer effect of these compounds. These compounds were evaluated for inhibition of aromatase enzyme of breast cancer in assistance by molecular docking simulations to understand molecular interaction between the enzyme and ligands. The IC50 values of compound 1 and 5 were found 138.27 ± 0.01 µl and 12.91 ± 0.01 µl, respectively, and both were found active due to their bulky structures in comparison to the active site of aromatase enzyme. The standard drug exemestane showed potent activity in comparison with the test compounds, having IC50 values of 0.052 ± 0.01 µl. Both compounds showed favorable electrostatic interactions with the active site of aromatase enzyme but the shape and steric bulk of the compounds was the limiting factor in their inhibitory effects. New lead compounds could be generated after extensive modifications guided by computational and experimental tools as a possible anticancer agents by targeting aromatase enzyme.

Safety profiling of pioglitazone and telmisartan combination by sub-chronic toxicity study in rat.

It has been reported that the major cause of mortality in diabetes is cardiovascular diseases and contribution of hypertension is significant in this context. Pioglitazone, a thiazolidinedione class of therapeutic agent is used to treat type 2 diabetes mellitus. Telmisartan, an angiotensin receptor blocker antihypertensive has been reported to have beneficial effect if co-administered with pioglitazone for the management of diabetes complications. The present research work aims to evaluate the safety/toxicity profile of this combination in rat model. The investigation was carried out after co-administering the drugs to the rats for 28 days at three dose levels of 50, 100 and 150 mg/kg covering low to high dose ranges. Various hematological and biochemical parameters were studied in addition to the histopathology of the major organs in order to evaluate the toxicity profile of the combination. Absence of mortality and histopathological changes as well as unaltered hematological and biochemical parameters was observed. This preliminary investigation concludes that the combination of pioglitazone and telmisartan can primarily be stated as safe in animals, even at the dose level which is several folds higher than the intended human dose. Thus, this combination can be explored in future to develop a rational therapy regimen to treat hypertensive diabetic patients.