Synthesis of thioether andrographolide derivatives and their inhibitory effect against cancer cells.

A series of novel thioether andrographolide derivatives were synthesized by incorporating various aromatic (or heteroaromatic) substituents into C-12 or 14-OH. A total of 38 andrographolide derivatives were prepared and evaluated for their in vitro inhibitory activity against cancer cells. All the derivatives exhibited better activity against prostate cancer cells (PC-3) than the parent compound. Among these, compounds 6a, 8, 9, 17, 19, 31, and 32 demonstrated good activity. These compounds were further evaluated for their anticancer activities against other cancer cell lines including MCF-7, MDA-MB-231, and A549. Compounds 31 and 32 showed excellent activity against MCF-7 with an IC50 value of 0.7 and 0.6 µM, respectively. The absolute configuration of 15a was determined via single-crystal X-ray diffraction. The activity of 6a (12S), which was the precursor of 15a, was better than that of the diastereoisomer 6b (12R). Moreover, the preliminary structure-activity relationship has been summarized. The results obtained herein are very important for further optimization of andrographolide.

Patterns of Comorbidity Among Girls With ADHD: A Meta-analysis.

CONTEXT: Although children with attention-deficit/hyperactivity disorder (ADHD) are at elevated risk for comorbid psychopathology, the clinical correlates of ADHD in girls are far less understood relative to boys, despite ADHD being one of the most common childhood disorders in girls. OBJECTIVE: To meta-analytically summarize rates of comorbid internalizing (anxiety, depression) and externalizing (oppositional defiant disorder [ODD], conduct disorder [CD]) psychopathology among girls with and without ADHD. DATA SOURCES: Literature searches (PubMed, Google Scholar) identified published studies examining comorbid psychopathology in girls with and without ADHD. STUDY SELECTION: Eighteen studies (1997 participants) met inclusion criteria and had sufficient data for the meta-analysis. DATA EXTRACTION: Odds ratios for each comorbid disorder were calculated from available data. Demographic (eg, age, race/ethnicity) and study characteristics (eg, referral source, diagnostic method) were also coded. RESULTS: Compared with girls without ADHD, girls with ADHD were significantly more likely to meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for each comorbid disorder assessed. Relative odds were higher for externalizing (ODD: 5.6×; CD: 9.4×) relative to internalizing disorders (anxiety: 3.2×; depression: 4.2×). Meta-regression revealed larger effect sizes of ADHD on anxiety for studies using multiple diagnostic methods, featuring younger children, and including clinic-referred (versus community-referred) girls; the effect of ADHD on ODD varied based on diagnostic informant. LIMITATIONS: Findings were derived from cross-sectional studies, precluding causal inferences. CONCLUSIONS: Girls with ADHD frequently exhibit comorbid externalizing and internalizing disorders. We discuss future research priorities and consider intervention implications for ADHD and comorbid psychopathology in girls.