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The scaffolds of two known CDK inhibitors (CAN508 and dinaciclib) were the starting point for synthesizing two series of pyarazolo[1,5‐a]pyrimidines to obtain potent inhibitors with proper selectivity. The study presented four promising compounds; 10d, 10e, 16a, and 16c based on cytotoxic studies. Compound 16a revealed superior activity in the preliminary anticancer screening with GI % = 79.02–99.13 against 15 cancer cell lines at 10 μM from NCI full panel 60 cancer cell lines and was then selected for further investigation. Furthermore, the four compounds revealed good safety profile toward the normal cell lines WI‐38. These four compounds were subjected to CDK inhibitory activity against four different isoforms. All of them showed potent inhibition against CDK5/P25 and CDK9/CYCLINT. Compound 10d revealed the best activity against CDK5/P25 (IC50 = 0.063 µM) with proper selectivity index against CDK1 and CDK2. Compound 16c exhibited the highest inhibitory activity against CDK9/CYCLINT (IC50 = 0.074 µM) with good selectivity index against other isoforms. Finally, docking simulations were performed for compounds 10e and 16c accompanied by molecular dynamic simulations to understand their behavior in the active site of the two CDKs with respect to both CAN508 and dinaciclib. [ABSTRACT FROM AUTHOR]

Background: Androgenetic alopecia (AGA) is a condition affecting both males and females. Aims We aimed to assess the demographic and clinical features of early‐onset AGA among smokers and nonsmokers and to evaluate whether prevalence of AGA was affected by smoking. Paatients/Methods: One thousand (1000) healthy males aged between 20 and 35 years not complaining of any local scalp condition and free of any mental illness were recruited for this study and divided into two groups of 500 each based on their smoking attitudes. Androgenetic alopecia was classified according to the Hamilton baldness scale, and trichoscopy was used to confirm the diagnosis of AGA. A designed questionnaire to determine basic physical and smoking habits completed and results was interpreted and analyzed. Results: The majority of smokers (425) had a form of AGA, while only (200) nonsmokers had a degree of AGA (P <.01). Of the smokers group, 235 (47%) had grade III AGA and 120 subjects (24%) had grade IV AGA. In the nonsmokers group, 100 subjects (20%) had grade II AGA and 50 subjects (10%) had either grade III or IV AGA. Conclusion: The prevalence of AGA among smokers was statistically higher than among nonsmokers, while severity of AGA was not associated with the intensity of smoking. Nicotine and its derivative cotinine might be responsible for accelerating AGA progress pending further validation. [ABSTRACT FROM AUTHOR]

Background: Cutaneous warts are frequent conditions that possess much challenge to treat. Objective: To evaluate safety and efficacy of intralesional injection of tuberculin purified protein derivative (PPD) antigen injection vs MMR (mumps, measles, rubella) antigen for the treatment of multiple warts. Methods: The study included 90 Patients who were divided into three groups (A, B, and C). Each group consisted of (30) patients. Group (A) subjects received intralesional PPD injections. Group (B) subjects received intralesional MMR antigen injection and Group (C) received intralesional saline injection. Results: Full clearance of warts was observed in 18 (60%) of patients in group (A) (70%) vs 24 patients (80%) in group (B). Distal warts completely disappeared in 18 (60%) of patients in group A and 12 (40%) of patients in group B. Infrequent side effects including pain, erythema, and minimal induration were reported in both groups. Conclusion: We established a good safety and efficacy profile for tuberculin PPD and MMR antigens in resistant wart treatment. [ABSTRACT FROM AUTHOR]

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