Antitubulin sulfonamides: The successful combination of an established drug class and a multifaceted target.

Tubulin, the microtubules and their dynamic behavior are amongst the most successful antitumor, antifungal, antiparasitic, and herbicidal drug targets. Sulfonamides are exemplary drugs with applications in the clinic, in veterinary and in the agrochemical industry. This review summarizes the actual state and recent progress of both fields looking from the double point of view of the target and its drugs, with special focus onto the structural aspects. The article starts with a brief description of tubulin structure and its dynamic assembly and disassembly into microtubules and other polymers. Posttranslational modifications and the many cellular means of regulating and modulating tubulin's biology are briefly presented in the tubulin code. Next, the structurally characterized drug binding sites, their occupying drugs and the effects they induce are described, emphasizing on the structural requirements for high potency, selectivity, and low toxicity. The second part starts with a summary of the favorable and highly tunable combination of physical-chemical and biological properties that render sulfonamides a prototypical example of privileged scaffolds with representatives in many therapeutic areas. A complete description of tubulin-binding sulfonamides is provided, covering the different species and drug sites. Some of the antimitotic sulfonamides have met with very successful applications and others less so, thus illustrating the advances, limitations, and future perspectives of the field. All of them combine in a mechanism of action and a clinical outcome that conform efficient drugs.

Determinants of smoking initiation among women in five European countries: a cross-sectional survey.

BACKGROUND: The rate of smoking and lung cancer among women is rising in Europe. The primary aim of this study was to determine why women begin smoking in five different European countries at different stages of the tobacco epidemic and to determine if smoking is associated with certain characteristics and/or beliefs about smoking. METHODS: A cross-sectional telephone survey on knowledge and beliefs about tobacco was conducted as part of the Women in Europe Against Lung Cancer and Smoking (WELAS) Project. A total of 5,000 adult women from France, Ireland, Italy, Czech Republic, and Sweden were interviewed, with 1,000 from each participating country. All participants were asked questions about demographics, knowledge and beliefs about smoking, and their tobacco use background. Current and former smokers also were asked questions about smoking initiation. Basic statistics on the cross-sectional data was reported with chi-squared and ANOVA p-values. Logistic regression was used to analyze ever versus never smokers. Linear regression analyses were used to analyze age of smoking initiation. RESULTS: Being older, being divorced, having friends/family who smoke, and having parents who smoke were all significantly associated with ever smoking, though the strength of the associations varied by country. The most frequently reported reason for initiation smoking was friend smoking, with 62.3% of ever smokers reporting friends as one of the reasons why they began smoking. Mean age of smoking initiation was 18.2 years and over 80% of participants started smoking by the age of 20. The highest levels of young initiators were in Sweden with 29.3% of women initiating smoking at age 14-15 and 12.0% initiating smoking younger than age 14. The lowest level of young initiators was in the Czech Republic with 13.7% of women initiating smoking at age 14-15 and 1.4% of women initiating smoking younger than age 14. Women who started smoking because their friends smoked or to look 'cool' were more likely to start smoking at a younger age. Women who started smoking to manage stress or to feel less depressed were more likely to start smoking at an older age. CONCLUSIONS: In all five participating countries, friends were the primary factor influencing ever smoking, especially among younger women. The majority of participants began smoking in adolescence and the average reported age of smoking initiation was youngest in Sweden and oldest in the Czech Republic.