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Background The heterocyclic compounds particularly pyridine displayed clinical and biological implementation. Pyridine scaffolds have been detected in most relevant drug molecules that included pyridine provided a great possibility for treatment. Main text Pyridine-containing compounds have increasing importance for medicinal application as antiviral, anticholinesterase activities, antimalarial, antimicrobial, antidiabetic and anticancer. This has generated concern among researchers in synthesising a variety of pyridine derivatives. Conclusion This review focuses on different pyridine targets as anticancer and their pharmacophoric elements controlling its activity.

Cyclin-dependent kinase inhibition is considered a promising target for cancer treatment for its crucial role in cell cycle regulation. Pyrazolo pyrimidine derivatives were well established for their antitumor activity via CDK2 inhibition. In this research, new series of pyrazolopyrimidine derivatives (4-15) was designed and synthesised as novel CDK2 inhibitors. The anti-proliferative activities against MCF-7, HCT-116, and HepG-2 were used to evaluate their anticancer activity as novel CDK2 inhibitors. Most of the compounds showed superior cytotoxic activity against MCF-7 and HCT-116 compared to Sorafenib. Only compounds 8, 14, and 15 showed potent activity against HepG-2. The CDK2/cyclin A2 enzyme inhibitory activity was tested for all synthesised compounds. Compound 15 showed the most significant inhibitory activity with IC 50 0.061 ± 0.003 µM. It exerted remarkable alteration in Pre G1 and S phase cell cycle progression and caused apoptosis in HCT cells. In addition, the normal cell line cytotoxicity for compound 15 was assigned revealing low cytotoxic results in normal cells rather than cancer cells. Molecular docking was achieved on the designed compounds and confirmed the two essential hydrogen binding with Leu83 in CDK2 active site. In silico ADMET studies and drug-likeness showed proper pharmacokinetic properties which helped in structure requirements prediction for the observed antitumor activity.

A new series of pyrido[2,3-d]pyrimidin-4(3H)-one derivatives having the essential pharmacophoric features of EGFR inhibitors has been designed and synthesised. Cell viability screening was performed for these compounds against A-549, PC-3, HCT-116, and MCF-7 cell lines at a dose of 100 μM. The highest active derivatives (8a, 8 b, 8d, 9a, and 12b) were selected for IC 50 screening. Compounds 8a, 8 b, and 9a showed the highest cytotoxic activities and were further investigated for wild EGFR WT and mutant EGFR T790M inhibitory activities. Compound 8a showed the highest inhibitory activities against EGFR WT and EGFR T790M with IC 50 values of 0.099 and 0.123 µM, respectively. In addition, it arrested the cell cycle at pre-G1 phase and induced a significant apoptotic effect in PC-3 cells. Furthermore, compound 8a induced a 5.3-fold increase in the level of caspase-3 in PC-3 cells. Finally, docking studies were carried out to examine the binding mode of the synthesised compounds against both EGFR WT and EGFR T790M .

To minimize the intrinsic toxicity of the antibacterial agent hydrazinyloxadiazole 1 , the hydrazine moiety was replaced with ethylenediamine (compound 7 ). This replacement generated a potent antifungal agent with no antibacterial activity. Notably, use of a 1,2-diaminocyclohexane moiety, as a conformationally-restricted isostere for ethylenediamine, potentiated the antifungal activity in both the cis and trans forms of N-(5-(2-([1,1’-biphenyl]-4-yl)-4-methylthiazol-5-yl)-1,3,4-oxadiazol-2-yl)cyclohexane-1,2-diamine (compounds 16 and 17 ). Both compounds 16 and 17 were void of any antibacterial activity; nonetheless, they showed equipotent antifungal activity in vitro to that of the most potent approved antifungal agent, amphotericin B. The promising antifungal effects of compounds 16 and 17 were maintained when assessed against an additional panel of 26 yeast and mold clinical isolates, including the Candida auris and C . krusei . Furthermore, compound 17 showed superior activity to amphotericin B in vitro against Candida glabrata and Cryptococcus gattii . Additionally, neither compound inhibited the normal human microbiota, and both possessed excellent safety profiles and were 16 times more tolerable than amphotericin B.

In the current work, some 1,3,4-oxadiazole-naphthalene hybrids were designed and synthesised as VEGFR-2 inhibitors. The synthesised compounds were evaluated in vitro for their antiproliferative activity against two human cancer cell lines namely, HepG-2 and MCF-7. Compounds that exhibited promising cytotoxicity (5, 8, 15, 16, 17, and 18) were further evaluated for their VEGFR-2 inhibitory activities. Compound 5 showed good antiproliferative activity against both cell lines and inhibitory effect on VEGFR-2. Besides, it induced apoptosis by 22.86% compared to 0.51% in the control (HepG2) cells. This apoptotic effect was supported by a 5.61-fold increase in the level of caspase-3 compared to the control cells. Moreover, it arrested the HepG2 cell growth mostly at the Pre-G1 phase. Several in silico studies were performed including docking, ADMET, and toxicity studies to predict binding mode against VEGFR-2 and to anticipate pharmacokinetic, drug-likeness, and toxicity of the synthesised compounds.

Background: Histone deacetylase inhibitors (HDACIs) are a relatively new class of potential drugs for treating cancer. Aim: Discovery of new anticancer agents targeting HDAC. Methods: New uracil and thiouracil derivatives panels were designed and synthesized as HDAC inhibitors. The synthesized compounds were tested against MCF-7, HepG2, and HCT-116. HDAC1 and HDAC4 inhibitory activities of these compounds were tested. The most active member was tested for its potential against cell cycle, apoptosis, caspase-3, and caspase-8. Docking studies were carried out against HDAC1. Results: Compounds 5a, 5b, 5f, 5i, 5k, and 5m exhibited promising cytotoxic activities. HDAC1 and HDAC4 inhibitory activities of these compounds were tested. Regarding the HDAC1 inhibitory activity, compound 5m was the most potent member (IC50 = 0.05 µg/mL) compared to trichostatin A (IC50 = 0.0349 µg/mL). For HDAC4, compound 5m showed superior activity (IC50 = 2.83 µg/mL) than trichostatin A (IC50 = 3.349 µg/mL). Compound 5m showed a high potential to arrest the HCT116 cell cycle at the G0-G1 phase. In addition, it showed an almost 17 times apoptotic effect (37.59%) compared to the control cells (2.17%). Furthermore, Compound 5m showed significant increases in the levels of caspase-3 and caspase-8. Finally, the uracil and thiouracil derivatives showed accepted binding mods against HDAC. Conclusions: Compound 5m has potential anticancer activity targeting HDAC with a significant apoptotic effect.

Background Full access to the frontal sinus is necessary for the effective treatment of some disorders affecting the frontal sinus, such as chronic frontal sinusitis [1,2]. This study aimed to evaluate the quality of life after endoscopic frontal sinus drill out procedures (Draf III. frontal drill out). Methods Thirty patients were admitted between June 2019 and June 2022 for Draf III as guided by endoscopic examination and CT information related to demographics, 22-item Sino-Nasal Outcome Test (SNOT-22) score, and endoscopic ostium assessment were recorded with a minimum follow-up of 6 months. Results There were 30 patients (13 men and 17 women, age range (20–60) years. Pathology of the frontal sinus disease was chronic rhinosinusitis with nasal polyposis (CRSwNP) (12 patients), chronic rhinosinusitis without nasal polyposis (CRSsNP) (11 patients), and (7) patients presented with other pathologies. We reported ostium patency 6 months postoperatively with patent frontal ostia in 54 out of 60 sinuses (90%). Patients had a significant improvement in the total mean SNOT-22 (40.62 ± 19.66) preoperatively and was reduced to (13.47 ± 10.87) 6 months postoperatively. In addition, each of its mean subscale scores was reduced. There was also significant SNOT-22 individual item level improvement postoperatively in all items. No major complications were recorded in our series. Conclusion In carefully selected patients with frontal sinus disease, Draf III procedure offers a very significant improvement in their quality of life.

Background Smoking is a major preventable risk factor for cardiovascular morbidity and mortality. Tobacco smoking induces atherosclerosis, ischemic heart diseases, and arrhythmias. The impact of electronic cigarettes on cardiovascular health is still controversial. This study aimed to evaluate the electrocardiographic parameters in chronic electronic cigarette users compared to chronic conventional cigarette smokers and a non-smoker control group of matched age and gender. Results The study involved 105 volunteers with no history of chronic or cardiovascular diseases or cardioactive drug use. Participants were assigned into three study groups, chronic e-cigarette users, conventional cigarette smokers, and non-smokers, each consisting of 35 participants. Demographic data, smoking history, vital signs, and 12-lead electrocardiogram (ECG) were evaluated. Demographic data were insignificantly different among all study groups. The mean heart rate was significantly higher in chronic electronic cigarette users and conventional cigarette smokers compared to non-smokers ( p  < 0.001).QRS complex duration was significantly shorter in e-cigarette users and conventional smokers compared to non-smokers ( p  < 0.001). Prolonged QT and QTc intervals duration were recorded in e-cigarette users and conventional smokers compared to non-smokers ( p  < 0.001). All the ventricular repolarization indices ( T wave—peak to T-end (Tpe) interval, TPe/QT ratio, and TPe/QTc ratio were significantly prolonged in chronic e-cigarette users, and conventional smokers compared to non-smokers ( p  < 0.001). Mean systolic, diastolic blood pressure, P wave amplitude and duration, and PR interval were insignificantly different between all groups ( P  > 0.05). Conclusions Chronic e-cigarette use is associated with higher heart rates, shorter QRS complex, prolonged QT, QTc duration, and prolonged ventricular repolarization indices compared to non-smokers of matched age and gender. Conclusively, e-cigarette use is associated with negative cardiovascular effects like conventional cigarette smoking.

A new series of pyrido[2,3-d]pyrimidin-4(3H)-one derivatives having the essential pharmacophoric features of EGFR inhibitors has been designed and synthesised. Cell viability screening was performed for these compounds against A-549, PC-3, HCT-116, and MCF-7 cell lines at a dose of 100 μM. The highest active derivatives (8a, 8 b, 8d, 9a, and 12b) were selected for IC50 screening. Compounds 8a, 8 b, and 9a showed the highest cytotoxic activities and were further investigated for wild EGFRWT and mutant EGFRT790M inhibitory activities. Compound 8a showed the highest inhibitory activities against EGFRWT and EGFRT790M with IC50 values of 0.099 and 0.123 µM, respectively. In addition, it arrested the cell cycle at pre-G1 phase and induced a significant apoptotic effect in PC-3 cells. Furthermore, compound 8a induced a 5.3-fold increase in the level of caspase-3 in PC-3 cells. Finally, docking studies were carried out to examine the binding mode of the synthesised compounds against both EGFRWT and EGFRT790M.A new series of pyrido[2,3-d]pyrimidin-4(3H)-one derivatives having the essential pharmacophoric features of EGFR inhibitors has been designed and synthesised. Cell viability screening was performed for these compounds against A-549, PC-3, HCT-116, and MCF-7 cell lines at a dose of 100 μM. The highest active derivatives (8a, 8 b, 8d, 9a, and 12b) were selected for IC50 screening. Compounds 8a, 8 b, and 9a showed the highest cytotoxic activities and were further investigated for wild EGFRWT and mutant EGFRT790M inhibitory activities. Compound 8a showed the highest inhibitory activities against EGFRWT and EGFRT790M with IC50 values of 0.099 and 0.123 µM, respectively. In addition, it arrested the cell cycle at pre-G1 phase and induced a significant apoptotic effect in PC-3 cells. Furthermore, compound 8a induced a 5.3-fold increase in the level of caspase-3 in PC-3 cells. Finally, docking studies were carried out to examine the binding mode of the synthesised compounds against both EGFRWT and EGFRT790M.

The discovery of novel antibacterial agents holds promise in mitigating the escalating threat of antimicrobial resistance (AMR). Guided by the structure-activity relationships (SAR) of our lead compound 1 against MRSA, we developed novel anti-MRSA compounds with a repositioned lipophilic tail from para to meta position. This strategic modification resulted in compounds 10e and 10l exhibiting equivalent activity to lead compound 1 (MIC = 4 µg/ml) against the highly clinically important strain MRSA USA300. Additionally, both compounds demonstrated a low propensity for resistance development and an acceptable cytotoxicity profile. However, their systemic administration was poorly tolerated. The in vivo study in a murine model revealed modest activity in the skin model but an acceptable effect in controlling systemic dissemination.