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Due to its rising antibiotic resistance and associated inflammations, Helicobacter pylori poses a challenge in modern medicine. Salvia officinalis , a member of the Lamiaceae family, is a promising medicinal herb. In this regard, a phytochemical screening followed by GC-MS and LC-MS was done to evaluate the chemical profile of the total ethanolic extract (TES) and the essential oil, respectively. The anti- H. pylori and the anti-inflammatory activities were evaluated by a micro-well dilution technique and COX-2 inhibition assay. Potential anti- H. pylori inhibitors were determined by an in silico study. The results revealed that the main metabolites were flavonoids, sterols, volatile oil, saponins, and carbohydrates. The LC-MS negative ionization mode demonstrated 12 compounds, while GC-MS showed 21 compounds. Carnosic acid (37.66%), epirosmanol (20.65%), carnosol1 (3.3%), and 12- O -methyl carnosol (6.15%) were predominated, while eucalyptol (50.04%) and camphor (17.75%) were dominant in LC-MS and GC-MS, respectively. TES exhibited the strongest anti- H. pylori activity (3.9 µg/mL) asymptotic to clarithromycin (0.43 µg/mL), followed by the oil (15.63 µg/mL). Carnosic acid has the best-fitting energy to inhibit H. pylori (-46.6769 Kcal/mol). TES showed the highest reduction in Cox-2 expression approaching celecoxib with IC 50 = 1.7 ± 0.27 µg/mL, followed by the oil with IC 50 = 5.3 ± 0.62 µg/mL. Our findings suggest that S. officinalis metabolites with anti-inflammatory capabilities could be useful in H. pylori management. Further in vivo studies are required to evaluate and assess its promising activity.

We describe the design and synthesis of two isatin-tethered quinolines series ( Q6a - h and Q8a - h ), in connection with our research interest in developing novel isatin-bearing anti-tubercular candidates. In a previous study, a series of small molecules bearing a quinoline-3-carbohydrazone moiety was developed as anti-tubercular agents, and compound IV disclosed the highest potency with MIC value equal to 6.24 µg/mL. In the current work, we adopted the bioisosteric replacement approach to replace the 3,4,5-trimethoxy-benzylidene moiety in the lead compound IV with the isatin motif, a privileged scaffold in the TB drug discovery, to furnish the first series of target molecules Q6a - h . Thereafter, the isatin motif was N -substituted with either a methyl or benzyl group to furnish the second series Q8a - h . All of the designed quinoilne-isatin conjugates Q6a - h and Q8a - h were synthesized and then biologically assessed for anti-tubercular actions towards drug-susceptible, MDR, and XDR strains. Superiorly, the N -benzyl-bearing compound Q8b possessed the best activities against the examined M. tuberculosis strains with MICs equal 0.06, 0.24, and 1.95 µg/mL, respectively.

Pimenta racemosa is a commonly known spice used in traditional medicine to treat several ailments. In this study, comprehensive phytochemical profiling of the essential oils and methanol extracts of P. racemosa leaves and stems was performed, alongside assessing their potential Helicobacter pylori inhibitory activity in vitro and in silico. The essential oils were chemically profiled via GC-MS. Moreover, the methanol extracts were profiled using HPLC-PDA-ESI-MS/MS. The antibacterial activity of the essential oils and methanol extracts against H. pylori was determined by adopting the micro-well dilution method. GC-MS analysis unveiled the presence of 21 constituents, where eugenol represented the major component (57.84%) and (59.76%) in both leaves and stems of essential oils, respectively. A total of 61 compounds were annotated in both leaves and stems of P. racemosa methanolic extracts displaying richness in phenolic compounds identified as ( epi )catechin and ( epi )gallocatechin monomers and proanthocyanidins, hydrolyzable tannin derivatives (gallotannins), flavonoids, and phenolic acids. The stem essential oil showed the most promising inhibitory effects on H. pylori, exhibiting an MIC value of 3.9 µg/mL, comparable to clarithromycin with an MIC value of 1.95 µg/mL. Additionally, in silico molecular modeling studies revealed that decanal, eugenol, terpineol, delta-cadinene, and amyl vinyl showed potential inhibitory activity on H. pylori urease as demonstrated by high-fitting scores indicating good binding to the active sites. These findings indicate that P. racemosa comprises valuable phytochemical constituents with promising therapeutic effects, particularly the stem, an economic agro-industrial waste.

This paper proposes a new blind, color image watermarking method using fast Walsh-Hadamard transformation (FWHT) and multi-channel fractional Legendre-Fourier moments (MFrLFMs). The input host color image is first split into 4 × 4 non-interfering blocks, and the MFrLFMs are computed for each block, where proper MFrLFMs coefficients are selected and FWHT is applied on the selected coefficients. The scrambled binary watermark has been inserted in the quantized selected MFrLFMs coefficients. The proposed method is a blind extraction, as the original host image is not required to extract the watermark. The proposed method is evaluated over many visual imperceptibility terms such as peak signal-to-noise ratio (PSNR), normalized correlation (NC), and bit error rate. The robustness of the proposed method is tested over several geometrical attacks such as scaling, rotation, cropping, and translation with different parameter values. The most widely recognized image processing attacks are also considered, e.g., compressing and adding noise attacks. A set of combination attacks are also tested to analyze the robustness of the proposed scheme versus several attacks. The proposed model's experimental and numerical results for invisibility and robustness were superior to the results of similar watermarking methods.

Streptococcus mutans has been considered as the major etiological agent of dental caries, mostly due to its arsenal of virulence factors, including strong biofilm formation, exopolysaccharides production, and high acid production. Here, we present the antivirulence activity of fatty acids derived from the endophytic fungus Arthrographis kalrae isolated from Coriandrum sativum against Streptococcus mutans . The chemical composition of the fatty acids was analyzed by gas chromatography-mass spectrometry GC-MS and revealed nine compounds representing 99.6% of fatty acids, where unsaturated and saturated fatty acids formed 93.8% and 5.8 % respectively. Oleic and linoleic acids were the major unsaturated fatty acids. Noteworthy, the fatty acids at the concentration of 31.3 mg L -1 completely inhibited Streptococcus mutans biofilm, and water insoluble extracellular polysaccharide production in both polystyrene plates, and tooth model assay using saliva-coated hydroxyapatite discs. Inhibition of biofilm correlated significantly and positively with the inhibition of water insoluble extracellular polysaccharide (R=1, p <0.0001). Furthermore, Arthrographis kalrae fatty acids at a concentration of 7.8 mg L -1 exhibited acidogenesis-mitigation activity. They did not show bactericidal activity against Streptococcus mutans and cytotoxic activity against human oral fibroblast cells at the concentration used. On the other hand, saliva-coated hydroxyapatite discs treated with sub-minimum biofilm inhibitory concentration of fatty acids showed disturbed biofilm architecture with a few unequally distributed clumped matrices using fluorescence microscopy. Our findings revealed that the intracellular fatty acid arrays derived from endophytic Arthrographis kalrae could contribute to the biofilm-preventing alternatives, specifically Streptococcus mutans biofilms.

Ammi majus L.; Family Apiaceae; is a plant indigenous to Egypt. Its fruits contain bioactive compounds such as furanocoumarins and flavonoids of important biological activities. An endophytic fungus was isolated from the fruits and identified as Aspergillus amstelodami (MK215708) by morphology, microscopical characterization, and molecular identification. To our knowledge this is the first time an endophytic fungus has been isolated from the fruits. The antimicrobial activity of the Ammi majus ethanol fruits extract (AME) and fungal ethyl acetate extract (FEA) were investigated, where the FEA showed higher antimicrobial activity, against all the tested standard strains. Phytochemical investigation of the FEA extract yielded five prenylated benzaldehyde derivative compounds isolated for the first time from this species: Dihydroauroglaucin (1), tetrahydroauroglaucin (2), 2-(3,6-dihydroxyhepta-1,4-dien-1-yl)-3,6-dihydroxy-5-(dimethylallyl)benzaldehyde (3), isotetrahydroauroglaucin )4), and flavoglaucin (5). Structure elucidation was carried out using (1H- and 13C-NMR). Fractions and the major isolated compound 1 were evaluated for their antimicrobial and antibiofilm activity. Compound 1 showed high antimicrobial activity against Escherichia coli with minimum inhibitory concentration (MIC) = 1.95 µg/mL, Streptococcus mutans (MIC = 1.95 µg/mL), and Staphylococcus aureus (MIC = 3.9 µg/mL). It exhibited high antibiofilm activity with minimum biofilm inhibitory concentration (MBIC) = 7.81 µg/mL against Staphylococcus aureus and Escherichia coli biofilms and MBIC = 15.63 µg/mL against Streptococcus mutans and Candida albicans and moderate activity (MBIC = 31.25 µg/mL) against Pseudomonas aeruginosa biofilm. This reveals that dihydroauroglaucin, a prenylated benzaldehyde derivative, has a broad spectrum antimicrobial activity. In conclusion, it was observed that the MICs of the FEA are much lower than that of the AME against all susceptible strains, confirming that the antimicrobial activity of Ammi majus may be due to the ability of its endophytic fungi to produce effective secondary metabolites.

Background and Objectives : Teeth decay and plaque are complicated problems created by oral pathogens. Tecoma stans (L.) and Cassia javanica (L.) are two ornamental evergreen plants widely distributed in Egypt. These plants are traditionally used for oral hygienic purposes. This study aims to elucidate the volatile oil constituents obtained from the flowers of these plants and evaluate the antimicrobial activity of these volatile oils against specific oral pathogens in comparison to chlorhexidine. Materials and Methods: The flowers obtained from both plants were extracted by n-hexane. GC-MS spectrometry was used to identify the constituents. Minimum inhibitory concentrations (MICs) were measured using tetrazolium salt (2,3-bis[2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide) (XTT). Results: GC-MS analysis revealed the presence of 32 and 29 compounds, representing 100% of the volatile constituents of Tecoma stans and Cassia javanica , respectively. The GC-MS analysis showed more than 60% of the volatile oil constituents are represented in both plants with different proportions. Chlorhexidine exerted stronger activity than tested plants against all microorganisms. Cassia javanica flower extract was more active against all tested microorganisms than Tecoma stans . Of note was the effect on Streptococcus mutans , which was inhibited by 100% at 12.5 and 25 µg/mL of Cassia javanica and Tecoma stans , respectively. The growth of Lactobacillus acidophilus was also completely inhibited by 25 µg/mL of the Cassia javanica extract. MIC90 and MIC were also calculated, which revealed the superiority of Cassia javanica over Tecoma stans against all tested oral pathogens. Conclusion: Cassia javanica flower volatile oils showed a potential anti-oral pathogen activity at relatively low concentrations. Also, Cassia javanica and Tecoma stans demonstrated a strong activity against tooth decay's notorious bacteria Streptococcus mutans . Both plants can be potential substituents to chlorhexidine. Formulating the constituents of these plants in toothpastes and mouthwashes as anti-oral pathogen preparations can be an interesting future plan.

Background: Antimicrobial resistance (AMR) is a global threat and the antimicrobial stewardship program (ASP) is a globally used tool to combat AMR. There is little information on the views among Pakistani physicians regarding AMR and the benefits of hospital antimicrobial stewardship implementation. This study was designed to explore the physicians' views about ASP. Methods: Qualitative face-to-face and telephonic interviews were conducted by using purposive sampling method with 22 physicians working in seven tertiary care public hospitals of Punjab, Pakistan. All interviews were audio recorded and transcribed verbatim. Qualitative software was used, and a thematic analysis was conducted. Results: Three broad themes were identified: (1) the growing concern of antimicrobial resistance in Pakistan, (2) the role(s) of healthcare professionals in antibiotic prescribing, and (3) managing antibiotic resistance in hospitals. Inadequate resources, poor healthcare facilities, and insufficiently trained medical staff were the major hurdles in ASP implementation in Pakistan. Conclusions: Our study found a poor familiarity of hospital ASP among physicians working in public sector tertiary care teaching hospitals, and a number of distinct themes emerged during this study that could be helpful in establishing the concept of hospital ASP in Pakistan. Overall, physicians showed a positive attitude towards the enforcement of ASP in all healthcare settings, including teaching hospitals.

Background : Community pharmacies are an integrated part of healthcare systems worldwide. In low and middle income countries like Pakistan, the paradigm of pharmacy practice is shifting from dispensing medicines to clinical activities. There are disparities in these practices according to location. Pharmacies in urban localities are better than those in rural areas. This qualitative study was conducted to explore patients' expectations and current practices in rural pharmacies. Methods : A cohort of adult pharmacy visitors (aged > 18 years) that reside in rural community was selected. Consenting participants were recruited by purposive sampling technique until thematic saturation level was achieved. A total of 34 patients were interviewed. Face-to-face interviews were conducted using a semi structured interview guide. All the data were transcribed and used to originate the themes. Results : On analysis, a total of 20 themes were obtained. Sixteen themes pronounced the current provided services. Four themes provided some suggestions for the development of better pharmacies. On call services to provide medicines, limited free extended pharmacy services, interest in patients' wellbeing, appropriate referral, vaccination, free medical camp, medical services at home, first aid, and counseling were appreciated by patients. Patients stated that medicines are inappropriately stored in unhygienic conditions, prices of medicines are comparatively high, and medicines are substandard. Unavailability of medicines, inept dispensing, limited staffing with poor knowledge, limited working hours, and quackery promotion are challenges in rural pharmacy practice. Patients say that non marginal pricing, informative services, new legislation, and proper vigilance by officials can improve the pharmacy services in rural communities. Conclusions : Patients alleged that rural pharmacies perform deprived practices. To improve service, new legislation and the proper implementation of existing law is needed.

Purpose : Patient satisfaction can identify specific areas of improvement in community pharmacy services. Currently in Pakistan, no evidence exists in this regard. This study was conducted to determine the needs of patients and the current standards of pharmacies. Methods : A cross-sectional study was conducted between October 2016 and June 2017. A pilot tested questionnaire was used to collected the data from 1088 patients of 544 community pharmacies. Likert scale and one way ANOVA was used to analyze the data. Results : The response rate of community pharmacies was 80% and that of purchasers was 68.1%. The mean age of participants was 35.2 years. The mean overall satisfaction score of participants was 2.78/5.00. Many patients were dissatisfied (1.65/5.00) with parking facilities provided by pharmacies. Pharmacy service time fulfilled the requirements of most patients (4.16/5.00). The counseling person's good attitude (3.99/5.00) was credited by purchasers. Level of patient satisfaction with the availability of medicines (3.19/5.00), safe storage of medicines in pharmacy stores (3.66/5.00), and quality of medicines (3.41/5.00) were almost moderate. Many patients were very satisfied (4.35/5.00) with readable instructions for their medications. Approximately half of the patients were dissatisfied with the waiting time. Many patients were also dissatisfied (2.28/5.00) with the knowledge of the counseling person. Patients perceived that staff interest in patient recovery (2.24/5.00) was low. No significant difference in level of satisfaction with regard to participant's characteristics was found. Conclusions : The current study demonstrated a low level of patient satisfaction with regard to community pharmacy services in Pakistan. These services need improvement.

We reported herein the synthesis, antifungal activity, docking and in silico ADME prediction studies of four novel series of sulfones 6a-f, 8a-c, 10a-f and 12a-c. All the newly synthesized sulfones were tested against four strains of Candida (including fluconazole-resistant Candida), two strains of Aspergillus, two dermatophytic fungi (Trichophytons mentagrophyte and Microsporum canis) and Syncephalastrum sp. with fluconazole as a reference drug. In general, compounds 8a and 10b showed selective and potent anticandidal activity (MIC: 0.19-0.81 µM) relative to fluconazole (MIC = 1.00 µM). Furthermore, 10e and 12a elicited a remarkable and selective antifungal activity against Aspergillus sp. and the dermatophytic fungi (MIC: 0.16-0.79 µM) relative to fluconazole (MIC: 2-2.6 µM). Moreover, the docking results of the sulfones 6a, 8a, 10a and 10b at the active site of CYT P450 14α-sterol demethylase showed a comparable binding interaction (interaction Energy = -34.87 to -42.43 kcal/mol) with that of fluconazole (IE = -40.37 kcal/mol).

Three series of 6-aryl-2-methylnicotinohydrazides 4a-i, N'-arylidene-6-(4-bromophenyl)-2-methylnicotino hydrazides 7a-f, and N'-(un/substituted 2-oxoindolin-3-ylidene)-6-(4-fluorophenyl)-2-methylnicotinohydrazides 8a-c were synthesized and evaluated for their potential in vitro antimycobacterial activity against M. tuberculosis. The results showed that isatin hydrazides 8a-c are remarkably more active than the parent hydrazide 4c. Hydrazides 8b and 8c exhibited the highest activity among all the tested compounds (MIC = 12.5 and 6.25 µg/mL, respectively). Compounds 8b and 8c were also devoid of apparent cytotoxicity to HT-29, PC-3, A549, HepG2 and MCF-7 cancer cell lines. Besides, 8b and 8c showed good drug-likeness scores of 0.62 and 0.41, respectively. Those two isatin hydrazides could offer an excellent framework for future development to obtain more potent antitubercular agents. The SAR study suggested that lipophilicity of the synthesized derivatives is a crucial element that accounts for their antimycobacterial activity. Finally, a theoretical kinetic study was established to predict the ADME of the active derivatives.

In continuation of our endeavor towards the development of potent and effective antimicrobial agents, three series of halophenyl bis-hydrazones (14a-n, 16a-d, 17a and 17b) were synthesized and evaluated for their potential antibacterial, antifungal and antimycobacterial activities. These efforts led to the identification of five molecules 14c, 14g, 16b, 17a and 17b (MIC range from 0.12 to 7.81 μg/mL) with broad antimicrobial activity against Mycobacterium tuberculosis; Aspergillus fumigates; Gram positive bacteria, Staphylococcus aureus, Streptococcus pneumonia, and Bacillis subtilis; and Gram negative bacteria, Salmonella typhimurium, Klebsiella pneumonia, and Escherichia coli. Three of the most active compounds, 16b, 17a and 17b, were also devoid of apparent cytotoxicity to lung cancer cell line A549. Amphotericin B and ciprofloxacin were used as references for antifungal and antibacterial screening, while isoniazid and pyrazinamide were used as references for antimycobacterial activity. Furthermore, three Quantitative Structure Activity Relationship (QSAR) models were built to explore the structural requirements controlling the different activities of the prepared bis-hydrazones.