Background: Quinoline- and quinolone-based compounds are important heterocyclic scaffolds investigated for diverse pharmacological applications. However, their structure–activity relationships (SARs), pharmacological profiles, and associated resistance mechanisms remain widely dispersed across the literature. Methods: A systematic review was conducted and reported in accordance with the PRISMA 2020 guidelines. Google Scholar, Google Patents, PubMed, Scopus, and Web of Science were searched for English-language, peer-reviewed articles published from 1 January 2020 to 29 August 2026. Original research articles with full texts available and compound-specific pharmacological, SAR, mechanistic, or resistance data were included. Of 312 identified records, 248 remained after duplicate removal; of these, 130 full-text articles were assessed, of which 34 were excluded, leaving 96 included studies. Results: The included studies investigated quinoline and quinolone derivatives for anticancer, antibacterial, antifungal, antiviral, anti-inflammatory, neurological and neuroprotective, cardiovascular and neurovascular, antimalarial and other antiprotozoal, antitubercular, and enzyme-inhibitory activities. Compound (60e) exhibited MICs of 0.5, 1, and 2 μg/mL against H37Rv, multidrug-resistant, and extensively drug-resistant Mycobacterium tuberculosis, respectively. Compound (162) retained an MIC of 0.125 μg/mL against three levofloxacin-resistant MRSA isolates, whereas levofloxacin showed MICs > 64 μg/mL. Compounds (130a) and (130b) showed potent antiplasmodial activity against chloroquine-resistant Plasmodium falciparum FcB1, with IC₅₀ values of 1.5 and 1.9 nM, respectively. Antiviral investigations identified quinolinone derivatives targeting HIV-1 integrase and the RNase H function of reverse transcriptase, alongside quinoline-based inhibitors of SARS-CoV-2 papain-like and main proteases. For antibacterial quinolones, resistance mechanisms included mutations in the quinolone resistance-determining regions of GyrA and ParC, plasmid-mediated quinolone resistance genes, and efflux pumps. Conclusions: Scaffold modifications, molecular hybridization, and functionalization at N-1, C-2, C-3, C-6, C-7, and C-8 were associated with changes in pharmacological activity and potency, depending on the scaffold, biological target, and assay system. These findings highlight the versatility of quinoline and quinolone scaffolds for pharmacological optimization and underscore the importance of understanding the structural determinants of activity and resistance.

Objective: To compare the efficacy, safety, weight reduction and treatment adherence of oral versus subcutaneous semaglutide in adults with uncontrolled T2DM and obesity. Methods: A multicenter retrospective cohort study was conducted between January 2023 and January 2024. Adult patients (≥18 years) with T2DM (HbA1c ≥ 7%) and obesity (BMI ≥ 30) who received either oral or subcutaneous semaglutide were included. Demographic, clinical, and biochemical variables including body weight, BMI, HbA1c, side effects, and adherence were extracted from electronic medical records. Adverse effects were categorized by severity. Comparative analyses between groups used Chi-square and Mann Whitney U tests, with p0.05). The severity of adverse effects predominantly gastrointestinal symptoms such as nausea, vomiting, constipation, and diarrhea did not differ significantly between groups (p=0.994). However, dizziness was significantly more frequent in the subcutaneous group (p = 0.04). Adherence was markedly higher with oral semaglutide (p<0.05), with cost identified as the primary barrier among oral users, while subcutaneous users more frequently cited side effects, forgetfulness, and limited weight loss. Weight reduction was comparable at 3 months (p=0.23), but significantly greater with oral semaglutide at 6, 9, and 12 months (all p<0.01). Conversely, HbA1c reduction favored subcutaneous semaglutide at 3 and 6 months (p=0.03 and 0.02), although baseline glycemic control was similar. Conclusions: This study demonstrates that while subcutaneous semaglutide may provide a faster early HbA1c decline, oral semaglutide offers superior long-term weight reduction and significantly better adherence, likely attributable to easier administration. Both formulations exhibited comparable safety profiles.