ABSTRACT
Multi-target directed ligands (MTDLs) have recently been popularized due to their outstanding efficacy in combating the complicated features of Alzheimer's disease. This study details the synthesis of piperazine-quinoline-based MTDLs through a multicomponent Petasis reaction, targeting multiple factors such as AChE, BuChE, metal chelation to restore metal dyshomeostasis, and antioxidant activity. Some of the synthesized compounds exhibited notable inhibitory activity against AChE and BuChE enzymes at specific concentrations. Among the synthesized compounds compound (95) containing a 4-chloroaniline moiety and a 4-methoxybenzyl group displayed the most promising inhibitory activities against AChE (IC50 3.013 µM) and BuChE (IC50 = 3.144 µM). Compound (83) featuring 2-methoxyaniline and 4-fluorobenzyl substituents, exhibited the highest BuChE inhibition (IC50 1.888 µM). Notably, compound (79) demonstrated 93-times higher selectivity for BuChE over AChE. Molecular docking and molecular dynamics simulations were also performed to explore the binding modes and stability of these compounds with the AChE amd BuChE proteins. Further, kinetics study was performed against AChE for comounds (83 and 95) which indicated mixed inhibition of the enzyme by these compounds, Amongs the synthesized compounds, nine compounds were assessed for their antioxidant activity, displaying significant antioxidant properties with IC50 values ranging from 156 µM to 310 µM. Moreover, all the compounds demonstrated metal chelating tendency with Cu+2, Zn+2, Fe+2, Fe+3 and Al+3. This study provides insights into the design of novel MTDLs, highlighting compound (95) as a potential candidate for combating Alzheimer's disease.
ABSTRACT
Introduction Undernutrition is one of the key determinants of morbidity and mortality in adolescent females worldwide and in India. Malnutrition, particularly undernutrition, is highly prevalent among adolescent females. Although undernutrition affects the health status of adolescent females leading to poor growth and developmental problem issues among them, still, the adolescent group remains to be neglected group. The present paper particularly focuses on challenges and ways forward for improving the nutritional status of adolescent females in Gujarat. Methods and material It's a mixed method study where the secondary data analysis was conducted comparing the National Family Health Survey-5 (NFHS-5) report with the Comprehensive National Nutritional Survey (CNNS) report for the assessment of undernutrition, overweight, and anemia status among adolescent females, and the primary assessment of the nutritional status of adolescent females across Gujarat was conducted through anthropometric measurements of height and weight. Results The NFHS-5 report findings showed total thinness among adolescent females (15-19 years) in Gujarat to be 52.5%, which increased by 3% from the NFHS-4 findings. Anemia among adolescent females has also been reported to be 69%, which also increased by 12.5% from the NFHS-4 findings. Tribal regions/populations had a higher prevalence of undernutrition. Being overweight among urban adolescent females was more prevalent than in rural regions. The key findings of the CNNS report also showed that 24% of adolescent females (10-19 years) were thin while 5% of adolescent females were overweight/obese in India, while in Gujarat, 8% of adolescent females were overweight/obese. The primary data gathered suggest a prevalence of overweight in Gujarat of 8.9% in adolescent females and total thinness of 50%. Conclusion The nutritional status of adolescent females is still a major concern in many parts of India. Considering the complex set of challenges to tackle malnutrition in Gujarat and with specific attention to the adolescent group, it is vital to understand district-specific challenges and plan, program, and design district-specific strategies and implement actions to improve the existing nutritional status of adolescent females.
