Technology for Gifted Students

This chapter proposes that software design using software with programming capabilities, such as Classroom Suite, is a good activity for gifted students to increase their science, technology, engineering, and mathematics (STEM) skills while designing appropriate learning activities for all students, including those with disabilities. The chapter describes design techniques that gifted students can apply during the development, offers as an example the design process for one of the authors' own Classroom Suite instructional games, and concludes with a description of several other games designed by the authors as further examples of the kinds of instructional software that gifted students can develop for students with disabilities using Classroom Suite.

Aralia armata roots: Extraction, isolation and molluscicidal activity against golden apple snails, Pomacea canaliculata

Aralia armata is one of the common herb species in mountainous areas, especially in the northern mountainous areas of Vietnam, which has potential in pharmaceutical and agricultural industries. Herein, we report that an oleanolic acid saponin named pseudogisenoside RT1 methyl ester (A) was isolated from the roots of the species Aralia armata. The fractionated extracts of dichloromethane, ethyl acetate, water and compound A were investigated for their molluscicidal effects, specifically on Pomacea canaliculata. The tests showed that the extracts and compound A from A. armata roots had good activity against P. canaliculata snail. In particular, compound A had a Lethal concentration of 50 (LC50) value of 16.443 µg/mL.

Synthesis and Evaluation of the Antibacterial and Antioxidant Activities of Some Novel Chloroquinoline Analogs

Quinoline heterocycle is a useful scaffold to develop bioactive molecules used as anticancer, antimalaria, and antimicrobials. Inspired by their numerous biological activities, an attempt was made to synthesize a series of novel 7-chloroquinoline derivatives, including 2,7-dichloroquinoline-3-carbonitrile (5), 2,7-dichloroquinoline-3-carboxamide (6), 7-chloro-2-methoxyquinoline-3-carbaldehyde (7), 7-chloro-2-ethoxyquinoline-3-carbaldehyde (8), and 2-chloroquinoline-3-carbonitrile (12) by the application of Vilsmeier–Haack reaction and aromatic nucleophilic substitution of 2,7-dichloroquinoline-3-carbaldehyde. The carbaldehyde functional group was transformed into nitriles using POCl3 and NaN3, which was subsequently converted to amide using CH3CO2H and H2SO4. The compounds synthesized were screened for their antibacterial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Streptococcus pyogenes. Compounds 6 and 8 showed good activity against E. coli with an inhibition zone of 11.00 ± 0.04 and 12.00 ± 0.00 mm, respectively. Compound 5 had good activity against S. aureus and P. aeruginosa with an inhibition zone of 11.00 ± 0.03 mm relative to standard amoxicillin (18 ± 0.00 mm). Compound 7 displayed good activity against S. pyogenes with an inhibition zone of 11.00 ± 0.02 mm. The radical scavenging activity of these compounds was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH), and compounds 5 and 6 displayed the strongest antioxidant activity with IC50 of 2.17 and 0.31 µg/mL relative to ascorbic acid (2.41 µg/mL), respectively. The molecular docking study of the synthesized compounds was conducted to investigate their binding pattern with topoisomerase IIβ and E. coli DNA gyrase B. Compounds 6 (−6.4 kcal/mol) and 8 (−6.6 kcal/mol) exhibited better binding affinity in their in silico molecular docking against E. coli DNA gyrase. The synthesized compounds were also found to have minimum binding energy ranging from −6.9 to −7.3 kcal/mol against topoisomerase IIβ. The SwissADME predicted results showed that the synthesized compounds 5–8 and 12 satisfy Lipinski’s rule of five with zero violations. The ProTox-II predicted organ toxicity results revealed that all the synthesized compounds were inactive in hepatotoxicity, immunotoxicity, mutagenicity, and cytotoxicity. The findings of the in vitro antibacterial and molecular docking analysis suggested that compound 8 might be considered a hit compound for further analysis as antibacterial and anticancer drug. The radical scavenging activity displayed by compounds 5 and 6 suggests these compounds as a radical scavenger.

Synthesis and Molecular Modeling Studies of 2-[2-(3-nitrophenyl)-1h-benzimidazol-1-yl]-acetamide Derivatives as Anthelmintic

Benzimidazole derivatives of substituted 2 [2-(3-nitrophenyl)-1H-benzimidazole-1-yl] acetamide analogues were synthesized and studied for antihelminthic activity. Compounds 3a–o were obtained in three steps, starting with the Oxidative Condensation of the appropriate 3-nitrobenzaldeyde, o-phenylenediamine and sodium hydrogen sulfite to form 2-(3-nitrophenyl)-1H-benzimidazole (1a). In second step Nucleophilic substitution, Chlorine atom of ethylchloroacetate will attach on nitrogen of benzimidazole by replacing hydrogen with elimination of hydrochloric acid to form ethyl [2-(3-nitrophenyl)-1H-benzimidazole-1-Yl acetate (2a).In third step amide formation from ester takes place by substitution of electrophilic with loss of ethanol to form substituted 2 [2-(3-nitrophenyl)-1H-benzimidazole-1-yl] acetamide 3a–o The antihelminthic activity showed that compounds 3f, 3h, 3i, 3j and 3k good activity against Indian earthworms (Pheretima posthuma) in comparison to albendazole.

Phytochemical Screening, Antibacterial, antifungal, and anthelmintic activity against plant pathogens of two Algerian plants: Pergularia tomentosa L. and Forsskaolea tenacissima L. from Oued Mzab (Northern Algerian Sahara)

Background: Plants are an abundant natural source of potential chemical compounds; they have been widely used in various industries, such as pharmaceuticals, cosmetics and food. This work aims to study two Saharan medicinal plants by evaluating the activity of plant extract against bacterial and fungal plant pathogens as well as against the model nematode Caenorhabditis (C.) elegans. Methods: The antimicrobial activity of plant extracts against plants pathogen is assessed in a 96-well plate assay by calculating the percentage of inhibition of bacteria. The antifungal activity against plant pathogenic fungi was evaluated by the agar diffusion method, inhibition was calculated by measuring the diameter of the inhibition zone. Anthelmintic activity was evaluated by calculating the average movement of C. elegans worms. Preliminary Phytochemical Screening is realized with HPTLC. Results: Hexane and ethyl acetate extract of Pergularia tomentosa showed broad-spectrum antimicrobial activity; this plant has the potential to act as a broad-spectrum antibacterial biopesticide. Hexane extract of Forsskaolea tenacissima exhibited good activity against one fungus. The extracts of Pergularia tomentosa showed good activity against Caenorhabditis elegans, the extracts of Forsskaolea tenacissima exhibited a low activity. Preliminary phytochemical screening with HPTLC shows that both plants are rich in steroids and flavonoids. Conclusion: Our study shows that the studied plants may possess a broad-spectrum antibacterial effect with a narrow-spectrum antifungal properties which can offer a more sustainable crop protection with a much safer environmental and human health impact. Plant extracts that inhibited C. elegans could provide a starting point for the development of new anthelmintic drugs.

Synthesis and Antimalarial Activity of 7-Chloro-4-(4-(2-(Oxo, Hydroxyl & Fluoro-2-1 (4-Phenyl)Ethyl)Piperazin-1-yl)Quinoline Derivatives

Since these days, microbes are resistant to the drugs available in the market, which has caused an alarming impact on society. 18 compounds in a series of 7-chloro-4-(piperazin-1-yl)quinoline derivatives were synthesized by nucleophilic addition reaction of piperazine with 4,7-dichloroquinoline followed by phenacyl bromides addition to heteroaryl piperazine and then reduction and fluorination. All 18 compounds were evaluated in vitro for their antimalarial activity against plasmodium falciparum strain. Although 12 compounds showed good activity, compound 3c was found to be more potent than standard drug Quinine having MIC 0.18 μg/ mL. On the other hand, 3d, 3e, 5a, and 5f were found to be equipotent (MIC 0.26 μg/ mL) to the standard drug.

Synthesis of chalcone-based pyrimidine derivatives and their antimicrobial activity

A series of substituted chalcones and pyrimidine derivatives on their base was synthesized. Obtained compounds were tested for antimicrobial activity and ability to increase activity of known antimicrobial substances. Pyrimidine products shown good activity against Staphylococcus aureus and Candida tropicalis. These compounds also could increase activity of modified polyguanidines against Staphylococcus aureus.

Synthesis, characterization and antimicrobial activity of novel tetrazoles clubbed with pyrimidine

An attempt was made to synthesize pyrimidine tetrazole derivatives of pharmaceutical interest by oxidative cyclization of chalcones with adequate yield and purity, prompted by the diversity of their wider usage and the fact that they are an integral part of genetic content. The present work involves the reaction of 5-(2,6-dimethylphenyl)-1H-tetrazole with acetic anhydride to yield 1-[5-(2,6-dimethylphenyl)-1H-tetrazol-1-yl] ethanone (1) and which then treated with different aromatic aldehydes in presence of alkaline medium to chalcones (2a-f). Reaction of chalcones (2a-f) with urea and thiourea to produce 5-[5-(2,6-dimethylphenyl)-1H-tetrazol-1-yl]-4-(substituted aryl ) pyrimidin-2-ol (3a-f) and 5-[5-(2,6-dimethylphenyl)-1H-tetrazol-1-yl]-4-(substituted aryl) pyrimidin-2-thiol (4a-f) respectively. All compounds were characterized by infrared spectroscopy (IR), H nuclear magnetic resonance (NMR), and mass spectrometry (MS) to prove the structure and assessed in vitro for their efficacy as antibacterial and antifungal activity against four bacteria. The compounds 3c, 3d and 3f and compounds 4c, 4d and 4f possess very good activity against and E. coli and the compounds 3e, 3c and 3a and compounds 4e,4b and 4c possess very good activity against fungi and .

CPX-351 Induction in Secondary Acute Myeloblastic Leukemia: Extended Follow up from the Italian Compassionate Use Program

Introduction: The outcome of patients with acute myeloid leukemia (AML) secondary to myelodisplastic syndrome (MDS) or therapy-related (t-AML) receiving conventional treatment and allogeneic stem cell transplantation consolidation (HSCT) is poor. CPX-351 is a new drug composed by liposomal encapsulated cytarabine and daunorubicin, at a fixed molecular ratio of 5:1. It showed superior results, compared to standard 3+7 induction, in a phase III trial (Lancet et al, JCO 2018) in patients affected by t-AML or AML with myelodisplasia-related changes and it is now commercially available for secondary AML (sAML). We recently published results from CPX-351 Italian Named (Compassionate) Use Program (CUP) which enrolled 73 elderly sAML patients (Guolo et al, Blood Cancer J. 2020) showing that CPX-351 is an effective induction regimen for high risk AML patients treated with a curative aim. With a limited follow up, our data suggested the good activity and tolerability of CPX-351. Good quality remissions with acceptable toxicity in the majority of patients was achieved and CPX-351 increased the feasibility of HSCT in a poor risk AML cohort. Scarce data are available on long term outcome of high risk patients receiving CPX-351 in the real life setting. Here we report the results from the extended follow up analysis of the Italian CUP. Results: Seventy three patients were enrolled between December 2018 and June 2019 in a compassionate use program (CUP) in 33 Italian Hematology Centers. Data collection began on July 2019 and included 71/73 patients (97.2%), enrolled in 31 Centers. As previously reported, median age was 65.5 years (52-79). Sixty-two (88%) patients had at least one relevant comorbidity upon enrollment. Six patients (9%) presented with ECOG 3-4 upon enrollment. With a median follow up of 22 months, median overall survival (OS) was 13 months (21.2 - 22.8 95% IC). Two-years OS was 28.6% in the whole cohort. In order to confirm the positive impact of HSCT in first complete remission (CR) and the correlation with the other variables, a landmark model was applied, including only patients alive and in CR at day 90. In landmark analysis, HSCT performed in first CR after CPX-351 was the only significant predictor of longer survival: median OS was not reached for patients transplanted in first CR Vs 12 months for patients who did not undergo HSCT, p < 0.05, Figure1). Two-year OS for patients who received HSCT was 57.6% vs 15.8% for patients who did not undergo HSCT. Conclusions: Results from the extended follow up of Italian CPX-351 CUP confirm the good activity CPX-351 in such a difficult cohort as sAML. Two-year OS for transplanted patients is high despite the high median age, the high frequency of severe comorbidities in this real life cohort of patients and the high frequency of high risk AML. On the contrary, non-transplanted patients show a poor outcome, thus confirming that CPX-351 induction as an optimal bridge to transplant induction therapy. Figure 1 Figure 1. Disclosures Galimberti: Incyte: Speakers Bureau; AbbVie, Janssen: Honoraria, Other: Travel grants. Marco: Insight,: Consultancy; Jazz: Consultancy; Janssen: Consultancy. Fracchiolla: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Speakers Bureau. Tafuri: Roche: Research Funding; Novartis: Research Funding; Celgene: Research Funding. Rossi: Novartis: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees. Pagano: Gilead Science, MSD, Pfizer, Basilea, Janssen, Novartis, Jazz Pharmaceutical, Cidara: Membership on an entity's Board of Directors or advisory committees; Menarini: Consultancy; Gilead Sciences, MSD, Pfizer Pharmaceuticals, Astellas Pharma: Speakers Bureau.

Bridge, N-heterocyclic Carbene Complexes with Silver (I) and Palladium (II): Synthesis and Biological Activity

The present study describes synthesis, characterization (UV-Vis, FT-IR, 1HNMR, CHN analysis and melting point) and biological activity of new substituted benzimidazolium salt and their N-heterocycliccarbene (NHC) respective Ag(I) and Pd(II) complexes. The benzimidazole reacted with acetamide substituents at 90oC to form variety substituted of benzimidazolium salt to yield unsymmetrically substituted salt. Silver(I) complex was synthesized from the reaction of unsymmetrical substituted benzimidazolium salt with Ag2O using in-situ deprotonation technique to give derived structures in good yield.The use of Ag(I)-NHC complex is as transfer reagents by using the transmetallation technique to prepare respective Pd(II)-NHC. The biological activity. of the formed substituted benzimidazolium salts, Ag(I) and Pd(II) complexes was estimated against some bacteria strains S. aureus. And E.coli .The Ag(I)showed good activity while their corresponding salt and Pd(II)-NHC complex show less activity.