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Abstract A novel series of six [1,2,4]triazolo[3,4-a]isoquinolin-3-yl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)prop-2-en-1-ones (3a–3f) was designed and synthesized. They were characterized based on spectral and elemental analyses. In silico studies were also committed to provide insights and a better understanding of their structural features. The six compounds were screened for their antiproliferative activity using the MTT assay against five human cancer cell lines, namely, A549, HCT116, PC3, HT29, and MCF-7 in parallel with the non-cancerous human lung cell line WI-38. The results showed that 3e and 3f have potential cytotoxic activities, especially on A549 cells with IC50 = 2.3 µM and 1.15 µM, respectively. Meanwhile, they recorded a minimal cytotoxic effect on WI-38 cells. Concerning the molecular mechanism of action, the present study showed the inhibitory effect of the six compounds against total EGFR. The most potent EGFR inhibitors were 3e and 3f with IC50 = 0.031 µM and 0.023 µM, respectively. The selectivity index of 3f for EGFRT790M was 1.81 times more selective than that of lapatinib. In addition, 3e and 3f initiated cell cycle arrest at the G2/M and pre-G1 phases along with the downregulation of anti-apoptotic protein Bcl2 and the upregulation of pro-apoptotic proteins: p53, Bax, and caspases 3, 8, and 9. Further studies are recommended to evaluate animal models’ promising anticancer activity and molecular mechanism of triazolo[3,4-a]isoquinoline derivatives 3e and 3f.

Abstract This study on Buddleja polystachya highlights its phytochemical composition, antimicrobial activity, and cytotoxic impacts. The study emphasizes the plant’s potential to treat ocular diseases by identifying important compounds involved in the bioactivity through GC-MS analysis. This study explores the antimicrobial and cytotoxic potential of Buddleja polystachya (stem and leaves) extracts, with a focus on their application in treating bacterial ocular infections and their efficacy against MCF7, HT29, and HepG2 cancer cells. Through comprehensive GC-MS analysis, a diverse array of phytochemicals was identified within Buddleja polystachya stem and leaves extracts, including carbohydrates, phenolic derivatives, fatty acids, and steroidal components. The extracts were then evaluated for their biological activities, revealing significant antimicrobial properties against a range of bacterial strains implicated in ocular infections. The research findings demonstrate that stem extracts derived from Buddleja polystachya demonstrated high to moderate cytotoxic effects on cancer cell lines MCF7, HT29, and HepG2. Notably, these effects were characterized by varying IC50 values, which suggest distinct levels of sensitivity. In contrast, leaf extracts exhibited reduced cytotoxicity when tested against all these cell lines, although they did so with a significantly higher cytotoxicity aganist HepG2 cells. The results of this investigation highlight the potential therapeutic utilization of Buddleja polystachya extracts in the management of ocular infections and cancer. These results support the need for additional research to elucidate the underlying mechanisms of action of these extracts and explore their potential as drugs.

Environmental conditions in hospitals facilitate the growth and spread of pathogenic bacteria on surfaces such as floors, bed rails, air ventilation units, and mobile elements. These pathogens may be eliminated with proper disinfecting processes, including the use of appropriate surface disinfectants. In this study, we aimed to evaluate of the antibacterial effects of seven surface disinfectants (HAMAYA, DAC, AJAX, Jif, Mr. MUSCLE, CLOROX, and BACTIL) against eight bacterial strains Klebsiella pneumoniae, Enterobacter aerogenes, Acinetobacter baumannii, Serratia marcescens, Escherichia coli, vancomycin-resistant Enterococcus faecalis-ATCC 51299, methicillin-resistant Staphylococcus aureus-ATCC 43300, and Pseudomonas aeruginosa-ATCC 1544, using two methods. The first was to determine the effective contact time of disinfectant against the tested bacterial strains, and the second was an assessment of the disinfection efficacy of each disinfectant on six types of contaminated surfaces with on a mixture of the eight tested bacterial strains. The results showed the efficacy of the disinfectants against the tested strains depending on the effective contact time. BACTIL disinfectant showed an efficacy of 100% against all tested strains at the end of the first minute of contact time. HAMAYA, DAC, Jif, Mr. MUSCLE, and CLOROX showed 100% efficiency at the end of the fourth, fifth, sixth, seventh, and fourteenth minutes, respectively, while AJAX disinfectant required nineteen minutes of contact time to show 100% efficacy against all tested strains.

Abstract The quality of olive fruit (OF) is widely affected due to geographical variation, affecting OF's chemical composition and biological properties. It is a novel and first-time study to evaluate the quality variation of 42 olive samples from different geographical origins based on phytochemical profile and their biological activities. The study reports the presence of unique chemical markers responsible for the difference in quality and biological activity of the olive samples. Biological activity (cytotoxic and antimicrobial) with GCMS phytochemical profile was evaluated. GCMS analysis confirmed the presence of 111 volatile compounds from various chemical classes with range (%) and average (%): esters (21.61–60.49) and 44.62, alcohols (20.73–49.2) and 38.06, hydrocarbons (3–38.88) and 15.39, ketones (0.16–3.87) and 0.75, acids (0.07–2.62) and 0.27, and aldehydes (0.12–1.47) and 0.45. The predominant ester was 13-methyl-pentadecanoic acid methyl ester, a differentiation marker between these samples. Cytotoxicity assay showed a significant inhibitory effect against MCF7 (8–64%) and HCT116 (0.11–44%) cell lines, whereas the extracts with the highest cytotoxicity observed were O17 (52.00 ± 2.00) and O25 (64.00 ± 4.88). The antimicrobial activity exhibited a range of zones of inhibition (mm) against P. aeruginosa (0.00–17.00), E. coli (0.00–15.00), S. aureus (0.00–13), and resistant S. aureus, i.e., MRSA (0.00–12.00). The extracts with the highest antimicrobial activity, i.e., O8 and O39 had identical MIC and MBC of 12.5 and 25 µg/ml against P. aeruginosa. In contrast, an MIC (50 and 25) and MBC (100 and 50) against E. coli were determined for O39 and O8. The statistical PCA and K-mean cluster analysis (P

Background: Surgical site infections (SSIs), especially when caused by multidrug-resistant (MDR) bacteria, are a major healthcare concern worldwide. For optimal treatment and prevention of antimicrobial resistance, it is important for clinicians to be aware of local drug-resistant bacterial pathogens that cause SSIs. Objective: To determine the frequency patterns of drug-resistant bacterial strains causing SSIs at a tertiary care hospital in Saudi Arabia. Methods: This retrospective study was conducted at the Microbiology laboratory of Al-Noor Specialist Hospital, Makkah, Saudi Arabia, and included wound swab samples from all cases of SSI between January 01, 2017, and December 31, 2021. The swabs were processed for the identification of bacterial strains and their resistance pattern to antibiotics according to the Clinical and Laboratory Standards Institute. Results: A total of 5409 wound swabs were analyzed, of which 3604 samples (66.6%) were from male. Most samples were from the Department of Surgery (43.3%). A total of 14 bacterial strains were isolated, of which 9 were Gram-negative bacteria. The most common isolates were Klebsiella pneumoniae, followed by Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), and vancomycin-resistant S. aureus (VRSA). In terms of MDR in 2021, the highest rate of carbapenem-resistance was in A. baumannii (97%). MDR was as follows: A. baumannii, 97%; K. pneumoniae, 81%; E. coli, 71%; MRSA, 60%; P. aeruginosa, 33%; VRE, 22%; and VRSA, 2%. Conclusion: This study showed that in the city of Makkah, Saudi Arabia, the rates of MDR bacteria are high, with the majority being Gram-negative.

Poetry has a prominent history in Arabic literature. The classical Arabic poetry has 16 m that vary in rhythm and target purpose. Chanting a poem eloquently requires knowing the poem’s meter and obtaining a diacritized version of its verses (letters inscribed with their short vowels); diacritics are often not inscribed in Arabic texts. This work proposes solutions to classify input Arabic text into the 16 poetry meters and prose. It also investigates the automatic diacritization of Arabic poetry. We adopt machine learning approach using a large dataset of 1657 k verses of poems and prose to develop neural networks to classify and diacritize Arabic poetry. We propose deep and narrow recurrent neural networks with bidirectional long short-term memory cells for solving these problems. The proposed model classifies the input text with an average accuracy of 97.27%, which is significantly higher than previous work. We also propose a solution that achieves an accuracy that approaches 100% when multiple verses of the same poem are available through predicting the class from the aggregate probabilities of the multiple verses. Diacritizing poetry is much harder than diacritizing prose due to the poet’s meticulous selection of phrases and relaxation of some diacritization rules.

The ESCRT pathway is crucial for membrane remodelling in eukaryotes. Here, Hatano et al. explore the phylogeny, structure, and biochemistry of homologues of the ESCRT machinery and the associated ubiquitylation system in Asgard archaea, the closest living relatives of eukaryotes.

Hydroxyapatite (HA) exhibits several desirable characteristics, but it still lacks osteoinduction, which is a necessary requirement for a bone scaffold. HA-based composites with different amounts of Bioglass® (BG) were prepared using spark plasma sintering (SPS). Careful selection of the SPS parameters avoided undesirable reactions between the calcium phosphate (CaP) and bioglass (BG present in the form of powder and fibres), as confirmed through X-ray diffraction analysis. Scanning electron microscopy images of the composite scaffolds revealed a fibre like appearance of the glassy region. The in vitro bioactivity and biodegradation analyses were performed by immersing the composites in simulated body fluid (SBF) and tris(hydroxymethyl)aminomethane (Tris), respectively. The ability to obtain only the CaP phase and glassy phase with desirable bioactive and biodegradation behaviour, indicated that these SPS scaffolds can be employed as bone scaffolds for clinical trials, after further in vivo analyses.

Chalcones are interesting anticancer drug candidates which have attracted much interest due to their unique structure and their extensive biological activity. Various functional modifications in chalcones have been reported, along with their pharmacological properties. In the current study, novel chalcone derivatives with the chemical base of tetrahydro-[1,2,4]triazolo[3,4-a]isoquinolin-3-yl)-3-arylprop-2-en-1-one were synthesized, and the structure of their molecules was confirmed through NMR spectroscopy. The antitumor activity of these newly synthesized chalcone derivatives was tested on mouse (Luc-4T1) and human (MDA-MB-231) breast cancer cell lines. The antiproliferative effect was evaluated through SRB screening and the MTT assay after 48 h of treatment at different concentrations. Interestingly, among the tested chalcone derivatives, chalcone analogues with a methoxy group were found to have significant anticancer activity and displayed gradient-dependent inhibition against breast cancer cell proliferation. The anticancer properties of these unique analogues were examined further by cytometric analysis of the cell cycle, quantitative PCR, and the caspases-Glo 3/7 assay. Chalcone methoxy derivatives showed the capability of cell cycle arrest and increased Bax/Bcl2 mRNA ratios as well as caspases 3/7 activity. The molecular docking analysis suggests that these chalcone methoxy derivatives may inhibit anti-apoptotic proteins, particularly cIAP1, BCL2, and EGFRK proteins. In conclusion, our findings confirm that chalcone methoxy derivatives could be considered to be potent drug candidates against breast cancer.

Infectious disease is one of the greatest causes of morbidity and mortality worldwide, and with the emergence of antimicrobial resistance, the situation is worsening. In order to prevent this crisis, antimicrobial resistance needs to be monitored carefully to control the spread of multidrug-resistant bacteria. Therefore, in this study, we aimed to determine the prevalence of infection caused by Klebsiella pneumoniae and investigate the antimicrobial profile pattern of K. pneumoniae in the last eleven years. This retrospective study was conducted in a tertiary hospital in Makkah, Saudi Arabia. Data were collected from January 2011 to December 2021. From 2011 to 2021, a total of 61,027 bacterial isolates were collected from clinical samples, among which 14.7% (n = 9014) were K. pneumoniae. The antibiotic susceptibility pattern of K. pneumoniae revealed a significant increase in the resistance rate in most tested antibiotics during the study period. A marked jump in the resistance rate was seen in amoxicillin/clavulanate and piperacillin/tazobactam, from 33.6% and 13.6% in 2011 to 71.4% and 84.9% in 2021, respectively. Ceftazidime, cefotaxime, and cefepime resistance rates increased from 29.9%, 26.2%, and 53.9%, respectively, in 2011 to become 84.9%, 85.1%, and 85.8% in 2021. Moreover, a significant increase in the resistance rate was seen in both imipenem and amikacin, with an average resistance rate rise from 6.6% for imipenem and 11.9% for amikacin in 2011 to 59.9% and 62.2% in 2021, respectively. The present study showed that the prevalence and drug resistance of K. pneumoniae increased over the study period. Thus, preventing hospital-acquired infection and the reasonable use of antibiotics must be implemented to control and reduce antimicrobial resistance.

This study evaluates the quality variation for twenty-seven capsicum fruit (CF) samples, in terms of their volatile oil composition and biological activities. The GCMS analysis revealed the presence of seventy one chemical compounds from different chemical classes with an average (%) composition of: 26.13 (alcohols) > 18.82 (hydrocarbons) > 14.97 (esters) > 3.08 (ketones) > 1.14 (others) > 1.07 (acids) > 0.72 (sugar) > 0.42 (aldehydes) > 0.15 (amino compounds). Alcohols and hydrocarbons were the most abundant in these CF samples with 1-Decanol, 2-octyl- and docosanoic acid, docosyl ester as the major components, respectively. The % inhibition in cytotoxicity assays was observed in the range of 9–47 (MCF7) and 4–41 (HCT116) whereas, the zone of inhibition (mm) for the antimicrobial activity was found to be 0.0–17 (P. aeruginosa) > 0.0–13 (E. coli and S. aureus). Moreover, the samples with the largest zone of inhibition in the agar-well-diffusion method (C16, C19, and C26) upon further evaluation presented the least MIC and MBC values against P. aeruginosa with an MIC and MBC (µg/mL) of 6.3 and 12.5, respectively. The outcome for GCMS and biological activities were further supported by statistical tools of PCA and K-mean cluster analysis which confirmed the C16 CF sample with the best activity followed by C5, C13 (the best cytotoxic), and C19, C26 (the best antimicrobial). The statistical analysis exhibited a high Chi-square value of 5931.68 (GCMS) and 32.19 (biological activities) with p = 0.00 for KMO and Bartlett’s Test of Sphericity. The 27-CF samples were effectively distinguished based on quality variation, and the C16 CF sample exhibited significant potential for further study.

The present work examines the influence of time delay introduced in the piezoelectric circuit of an excited Duffing harvester device with hardening stiffness on the vibration and voltage amplitudes. Specifically, we seek to exploit a delayed electrical circuit of the harvester to enhance its performance. We consider the case of a monostable system and we use a perturbation technique to approximate the periodic response and the corresponding voltage amplitude near the principal resonance. It is shown that for appropriate values of delay amplitude, the energy harvesting performance is improved over a certain range of coupling parameters and excitation frequencies. Numerical simulation is conducted to support the analytical predictions.

Hydrazonyl bromides 2a,b reacted with active methylene compounds (dibenzoylmethane, acetylacetone, ethyl acetoacetate, phenacyl cyanide, acetoacetanilide, ethyl cyanoacetate, cyanoacetamide and malononitrile) to afford the corresponding 1,3,4,5- tetrasubstituted pyrazole derivatives 5-12a,b. Reaction of 12a,b with formamide, formic acid and triethyl orthoformate give the pyrazolo[3,4-d]pyrimidine, pyrazolo[3,4- d]pyrimidin-4(3H)one and 5-ethoxymethylene-aminopyrazole-4-carbo-nitrile derivatives 13-15a,b, respectively. Compounds 15a,b reacted with benzhydrazide and hydrazine hydrate to afford pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine and [4-iminopyrazolo- [3,4-d]pyrimidin-5-yl]amine derivatives 16a,b and 17a,b. Reactions of compounds 17a,b with triethyl orthoformate and carbon disulfide give the corresponding pyrazolo[4,3-e]- [1,2,4]triazolo[1,5-c]pyrimidine derivatives 18a,b and 19a,b, respectively.

Several 1,3-diaryl-5-(cyano-, aminocarbonyl- and ethoxycarbonyl-)-2-pyrazoline, pyrrolo[3,4-c]pyrazole-4,6-dione and 1,3,4,5-tetraaryl-2-pyrazoline derivativeswere prepared by the reaction of nitrilimine with different dipolarophilic reagents. The newcompounds were characterized using IR, 1H-NMR, 13C-NMR and mass spectra. Biologicalscreening of some compounds is reported.

2-Thioxopyrimidinyl-5-(N,N-dimethylamino)formamidine (5) and 1,3-diphenyltriazolo[3,4-d]pyrimidinyl-N,N-dimethylformamidine (14) were prepared by condensation of 6-amino-2-thioxo-1,3-dihydropyrimidin-4-one (2) and 7-amino-1,3-diphenyl-1,2,4-triazolo[4,3-a]pyrimidin-4-one (13) with dimethylformamide dimethyl-acetal (DMFDMA). Compound 5 reacts with acetophenone and 2-acetylthiophene to give the 2-thioxo-1,3-dihydropyridino[2,3-d]pyrimidin-4-ones 3a and 3b, respectively. Compounds 3a,b react with hydrazonoyl halides 6,7 to give pyridino[2,3-d]triazolo[4,5-a]pyrimidin-4-ones 11a-d and not the isomeric structures 12a-d. Formamidines of type 14 react with ethyl cyanoacetate, malononitrile and benzoyl acetonitrile to give the 1,3-diphenyl-3a-hydropyridino[2,3-d]1,2,4-triazolo[4,5-a]pyrimidin-4-one derivatives 15a,b and 18, respectively. The structures of the newly synthesized compounds are established on the basis of chemical and spectroscopic evidences as well as their synthesis by alternative methods.

Arylidenesulfonylacetonitriles react in acetonitrile with 1-methylisoquinoline and isoquinolin-1-yl-acetonitrile in the presence of piperidine to give benzo[a]quinolizines 6,9 and 7,10, respectively. The structures of the products were established on the basis of elemental and spectral analyses and their chemical reactivity.

Reaction of 1,2-dihydro-2-thioxopteridin-4(3H)-one, 6,7-dimethyl-1,2-dihydro-2-thioxopteridin-4(3H)-one and 6,7-diphenyl-1,2-dihydro-2-thioxopteridin-4(3H)-one with hydrazonoyl halides affords the title compounds in good yields.

The preparation of highly efficient and low-cost activated carbon from sawdust was achieved for the treatment of uranium-contaminated groundwater. The adsorption properties of the synthesized activated carbon, as well as their ability to be reused, were assessed. The obtained results demonstrated that sawdust activated carbon (SDAC) and its amine form (SDACA) had high affinity towards uranium ions at pH values of 4.5 and 5 for SDAC and SDACA, respectively. The experimental results showed that the maximum adsorption capacity of uranium was 57.34 and 76.7 mg/g for SDAC and SDACA, respectively. A maximum removal efficiency of 89.72% by SDAC and 99.55% by SDACA were obtained at a solid/liquid ratio of 8 mg/mL. The removal mechanism of uranium by SDAC and SDACA was suggested due to interaction with the amine and carboxylic groups. The validation of the method was verified through uranium separation from synthetic as well as from groundwater collected from water wells in the Wadi Naseib area, Southwestern Sinai, Egypt.

We explore quasi-periodic (QP) vibration-based energy harvesting (EH) in a forced nonlinear oscillator under time delay. The energy harvesting system consists in a delayed Duffing oscillator subject to harmonic excitation coupled to an electric circuit through an electromechanical coupling mechanism.We consider the case of primary resonance for which the frequency of the excitation is near the natural frequency of the oscillator. Application of the double-step perturbation method enables the approximation of the amplitude of the QP vibrations used to extract the average powers from the harvester device. Results shown that for a small value of delay amplitude, the periodic vibration-based EH can be extracted in a narrow range near the resonance, while QP vibration-based EH can be extracted over broad ranges of excitation. For relatively increasing value of the delay amplitude, only QP vibration-based EH can be extracted.

The reductive perturbation method has been employed to derive the Korteweg-de Vries (KdV) equation for small- but finite-amplitude electrostatic ion-acoustic waves in weakly relativistic plasma consisting of warm ions and isothermal electrons. An algebraic method with computerized symbolic computation is applied in obtaining a series of exact solutions of the KdV equation. Numerical studies have been made using plasma parameters which reveal different solutions, that is, bell-shaped solitary pulses, rational pulses, and solutions with singularity at finite points, which called “blowup” solutions in addition to the propagation of an explosive pulses. The weakly relativistic effect is found to significantly change the basic properties (namely, the amplitude and the width) of the ion-acoustic waves. The result of the present investigation may be applicable to some plasma environments, such as ionosphere region.