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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]

Design and synthesis of three novel series of aryl enaminones (3a–f and 5a–c) and pyrazole (4a-c) linked compounds with sulphonamides, sulfaguanidine, or carboxylic acid functionalities were reported as carbonic anhydrase inhibitors (CAIs) using the "tail approach" strategy in their design to achieve the most variable amino acids in the middle/outer rims of the hCAs active site. The synthesised compounds were assessed in vitro for their inhibitory activity against the following human (h) isoforms, hCA I, II, IX, and XII using stopped-flow CO2 hydrase assay. Enaminone sulphonamide derivatives (3a–c) potently inhibited the target tumour-associated isoforms hCA IX and hCA XII (KIs 26.2–63.7 nM) and hence compounds 3a and 3c were further screened for their in vitro cytotoxic activity against MCF-7 and MDA-MB-231 cancer cell lines under normoxic and hypoxic conditions. Derivative 3c showed comparable potency against both MCF-7 and MDA-MB-231 cancer cell lines under both normoxic ((IC50 = 4.918 and 12.27 µM, respectively) and hypoxic (IC50 = 1.689 and 5.898 µM, respectively) conditions compared to the reference drug doxorubicin under normoxic (IC50 = 3.386 and 4.269 µM, respectively) and hypoxic conditions (IC50 = 1.368 and 2.62 µM, respectively). Cell cycle analysis and Annexin V-FITC and propidium iodide double staining methods were performed to reinforce the assumption that 3c may act as a cytotoxic agent through the induction of apoptosis in MCF-7 cancer cells. [ABSTRACT FROM AUTHOR]

The article discusses the role of histone acetyltransferase enzymes (HATs) and histone deacetylases (HDACs) in regulating epigenetic processes that affect gene transcription and genomic stability. HDACs, in particular, have been the focus of drug discovery for cancer therapy, with several inhibitors already approved. Current research is focused on developing selective inhibitors for different subtypes of HDACs. The article also explores the use of protein degradation through proteolysis targeting chimera (PROTAC) as a new approach for inhibiting physiological processes. The Special Issue highlights various studies on the development and biological characterization of HDAC and HAT inhibitors, as well as their therapeutic efficacy in combination with other drugs. [Extracted from the article]

Telemedicine involves distant exchange of medical information between health providers and patients via a telecommunication device with/without the aid of an audiovisual interactive assistance. The current COVID 19 pandemic impact on health services mandated an utmost readiness to implement telemedicine which in part is dependent on health care providers willingness to adopt such platforms. The aim of this cross sectional study was to assess knowledge and attitude toward telemedicine Egyptian dermatologists amidst the COVID 19 pandemic. A cross sectional study was designed and data were collected using structured self-administered online questionnaires. Dermatologists had a good knowledge about telemedicine (mean 4.17 ± 1.63; p <.05). Of those completing the questionnaire, 193 (68.9%) were familiar with the term 'telemedicine' and 164 (58.6%) were familiar with tools like teleconferencing. The majority of responding dermatologists 227 (81.1%) were confident that the COVID 19 pandemic is a good opportunity to start applying telemedicine protocols however the majority 234 (83.6%) preferred using it on trial basis at first before full implementation. In conclusion an overall good attitude toward telemedicine was reported with a mean of 3.39 (p <.05). Further large scale studies are required to verify such findings. [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]

Pursuing on our efforts toward searching for efficient hCA IX and hCA XII inhibitors, herein we report the design and synthesis of new sets of benzofuran-based sulphonamides (4a,b, 5a,b, 9a–c, and 10a–d), featuring the zinc anchoring benzenesulfonamide moiety linked to a benzofuran tail via a hydrazine or hydrazide linker. All the target benzofurans were examined for their inhibitory activities toward isoforms hCA I, II, IX, and XII. The target tumour-associated hCA IX and XII isoforms were efficiently inhibited with KIs spanning in ranges 10.0–97.5 and 10.1–71.8 nM, respectively. Interestingly, arylsulfonehydrazones 9 displayed the best selectivity toward hCA IX and XII over hCA I (SIs: 39.4–250.3 and 26.0–149.9, respectively), and over hCA II (SIs: 19.6–57.1 and 13.0–34.2, respectively). Furthermore, the target benzofurans were assessed for their anti-proliferative activity, according to US-NCI protocol, toward a panel of sixty cancer cell lines. Only benzofurans 5b and 10b possessed selective and moderate growth inhibitory activity toward certain cancer cell lines. [ABSTRACT FROM AUTHOR]

On account of their significance as apoptosis inducing agents, merging indole and 3-hydrazinoindolin-2-one scaffolds is a logic tactic for designing pro-apoptotic agents. Consequently, 27 hybrids (6a-r, 9a-f and 11a-c) were synthesised and evaluated for their cytotoxicity against MCF-7, HepG-2 and HCT-116 cancer cell lines. SAR studies unravelled that N-propylindole derivatives were the most active compounds such as 6n (MCF-7; IC50=1.04 µM), which displayed a significant decrease of cell population in the G2/M phase and significant increase in the early and late apoptosis by 19-folds in Annexin-V-FTIC assay. Also, 6n increased the expression of caspase-3, caspase-9, cytochrome C and Bax and decreased the expression of Bcl-2. Moreover, compounds 6i, 6j, 6n and 6q generated ROS by significant increase in the level of SOD and depletion of the levels of CAT and GSH-Px in MCF-7. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is a highly aggressive malignancy with limited treatment options due to its heterogeneity and the lack of well-defined molecular targets. In our endeavour towards the development of novel anti-TNBC agents, herein we report a one-pot three-component synthesis of novel spirooxindoles 6a-p, and evaluation of their potential anti-proliferative activity towards TNBC MDA-MB-231 cells. Spirooxindoles 6a, 6e and 6i emerged as the most potent analogues with IC50 = 6.70, 6.40 and 6.70 µM, respectively. Compounds 6a and 6e induced apoptosis in MDA-MB-231 cells, as evidenced by the up-regulation of the Bax and down-regulation of the Bcl-2, besides boosting caspase-3 levels. Additionally, 6e displayed significant increase in the percent of annexin V-FITC positive apoptotic cells from 1.34 to 44%. Furthermore, spirooxindoles 6e and 6i displayed good inhibitory activity against EGFR (IC50 = 120 and 150 nM, respectively). Collectively, these data demonstrated that 6e might be a potential lead compound for the development of effective anti-TNBC agents. [ABSTRACT FROM AUTHOR]