RESUMO
Four series of tetrahydro-2H-1,3,5-thiadiazine thione derivatives were screened for their in vitro antiproliferative activities against two human cancerous PC3 and HeLa cell lines. The cytotoxicity of all the compounds (series A-D) was also determined on mammalian mouse fibroblast 3T3 cells. Most of the compounds showed significant anticancer potential against both cancer cell lines within the range of IC50 = 6.4-29.9 and 2.4-23.8 M respectively when compared with standard doxorubicin (IC50 = 0.3 M). All compounds demonstrated a notable selectivity for Hela cells and found either non-toxic or relatively less toxic for 3T3 cell lines model. The structure-activity relationship indicated that antiproliferative activity mainly influenced by the nature and position of substituents at thidiazine nucleus. In general, the presence of aryl groups for example 3,4-(OMe) 2.Bzl and CH(Ph)Me at N-3 position resulted in a significant activity. Under enzymatic hydrolysis, complete conversion (100%) of ester derivative of thiadiazine thione (10a) into its acidic counterpart (7c) was achieved during 20 min which indicated that these types of THTT ester derivatives can be a possible lead for future investigations as prodrug anticancer probes.
Assuntos
Proliferação de Células/efeitos dos fármacos , Pró-Fármacos/farmacologia , Tiazinas/farmacologia , Tionas/farmacologia , Células 3T3/efeitos dos fármacos , Animais , Células HeLa/efeitos dos fármacos , Humanos , Camundongos , Células PC-3/efeitos dos fármacos , Ratos , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: To evaluate the performance of first-trimester preeclampsia-screening algorithm in predicting preeclampsia (PE). STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Obstetrics and Gynaecology, Combined Military Hospitals (CMH) Lahore, Pakistan, between 1st January and 31st August 2022. METHODOLOGY: Data of 100 women of any parity aged 18-35 years at gestational age < 13 weeks based on the last menstrual period (LMP), was analysed. First trimester Fetal Medicine Foundation (FMF) screening algorithm for preeclampsia was used entering maternal characteristics, mean arterial pressure and uterine pulsatility index only, for risk calculation. Patients were followed up till delivery for the development of preeclampsia and fetomaternal outcomes. Clinical characteristics of women with and without preeclampsia were compared using the Chi-square and independent samples t-test. RESULTS: The mean age of patients was 29.29±4.56 years and 60% were nullipara. Seventy-eight patients were placed in the low-risk category and 22 patients were in the high-risk category according to the FMF algorithm. Preeclampsia developed in 13 patients. For a risk cut-off of 1 in 100, the FMF algorithm showed a detection rate of 38% with diagnostic accuracy of 75% and a false positive rate (FPR) of 20%. CONCLUSION: Although the performance of adapted FMF algorithm to predict preeclampsia gestational was low, it was found superior to prediction by maternal risk factors alone. Adjustment for additional factors or ethnicity-specific values may help in further improvement of detection rate. KEY WORDS: Blood pressure, Biomarkers, Biological markers, Preeclampsia, Risk assessment.