Structural variation in π-conjugated DNA binders through click chemistry: synthesis and interaction studies

This thesis presents the design, synthesis and physical studies of new structurally-varied cationic oligoheteroaromatic DNA binders in six chapters. Chapter 1 introduces DNA and its importance in modern science such as genetic and medicinal research. The interactions of DNA with small molecules are also discussed. A description is provided of click chemistry, a method for the synthesis and design of structurally-varied molecules, in this case designed to interact with DNA. Chapter 2 presents the synthesis of alkyne-substituted oligoheteroaromatic compounds by means of bromination, iodination, and Suzuki, Stille and Sonogashira cross-coupling reactions. These alkyne-substituted oligoheteroaromatic compounds were designed to be used as building blocks for click reactions. Chapter 3 describes the synthesis of azide-substituted oligoheteroaromatic compounds from amines by means of a safe method. The Pd-catalysed cross-coupling of azidesubstituted building blocks to form oligoheteroaromatics is also described. The azidesubstituted oligoheteroaromatic compounds were designed as building blocks complementary to the alkyne-substituted compounds described in Chapter 2. Chapter 4 presents the synthesis and characterisation of new π-conjugated molecules utilising click chemistry between alkyne- and azide-substituted compounds leading to a series of structurally-varied di- and tricationic oligoheteroaromatic putative DNA binders. Chapter 5 describes DNA-binding studies for the di- and tricationic oligoheteroaromatic compounds using a variety of biophysical techniques to quantify DNA binding and elucidate binding modes. Additionally, this chapter presents results from preliminary V exploration of the sequence selectivity of our cationic oligoheteroaromatics by comparing binding affinities and binding modes for two different sequences of DNA, viz. poly(dGdC)40 and poly(dA)80poly(dT)80. Chapter 6 presents the preliminary synthetic and DNA-binding studies of selected extended cationic oligoheteroaromatic compounds. Finally, this chapter presents the overall conclusions of the study, including selected comments and suggestions about future studies and applications

Impact Of COVID-19 Pandemic On The Pattern Of Azithromycin Prescribing; A Review

Objective: Emergence of COVID-19 infection and its persistence globally for three years in a row (2020-2022) entailed several modifications in healthcare services, among which drug prescribing was an important outcome. This review aims to highlight changing trends in azithromycin prescribing during pandemic years. Methods: PubMed database was systematically searched for combinations of the following keywords: Antibiotics; Antimicrobial resistance; Azithromycin; COVID-19. Results: A total of 12 articles were included in this review. All included studies demonstrated a notable increase in azithromycin consumption during COVID-19 pandemic in Spain, Brazil, USA, India, Croatia, and Jordan. Healthcare systems worldwide should be prepared to address anticipated outcomes of increased azithromycin use particularly possible changing trends in azithromycin resistance, and systemic side effects of the drug

Tobacco Smoking, Secondhand Smoke Exposure and Cessation Perceptions by Dental Students in Al Madinah, a Conservative Saudi Society

Objective: To explore the prevalence of tobacco use and secondhand smoke (SHS) exposure in dental students and to investigate their perceptions on the role of dentists in tobacco cessation activities. Material and Methods:  A questionnaire-based study was conducted in a public university in Al Madinah, Saudi Arabia. The questionnaire investigated demographic factors, tobacco use practices, SHS exposure, and student perceptions of tobacco cessation activities. Descriptive statistics and statistical significance of differences between demographic groups were calculated. Results: A total of 228 students participated with 43.0% (n=98) males and 57.0% (n=130) females. A proportion of 30.7% (n=70) of the participants smoked tobacco, and these constituted 51 males (73%) and 19 females (27%). Only 39 students (15 females and 24 males) indicated their method of tobacco use, which was mainly cigarettes and waterpipes. One in two students was exposed to SHS. Non-smokers had better awareness of the health hazards of SHS (p<0.001), and were more likely to adopt tobacco cessation activities recommended by dentists (p<0.05). Conclusion:  A substantial proportion of dental students in a very conservative religious area smoke tobacco and are exposed to SHS. Their perceptions of the harms of SHS and attitudes on cessation need improvement. The influence of culture and religion in shaping health risk behaviors in conservative communities needs to be verified