Synthesis of novel cyanoacetamides derivatives and their urease inhibition studies

The present study reports a convenient approach for the synthesis of cyanoacetamide based derivatives (7-27) via two-step process involving Knoevenagel reaction, followed by three component reaction to avail desired compounds. All the synthesized compounds were obtained in good to excellent yield and extensively characterized employing 1H NMR, 13C NMR, mass spectrometry and physical parameters. Further, these compounds were screened for urease inhibition. All of the synthesized compounds exhibited good to excellent urease activity notably compound 15 and 19 showed excellent urease inhibition activity with IC50 value ~17.34 μg/mL and 36.75 μg/mL in comparison to thiourea (used as standard) having IC50 value ~27.5 μg/mL

The H Syndrome: A Genodermatosis

H syndrome (histiocytosis lymph adenopathy plus syndrome) is an autosomal recessive disorder caused by mutations in the SLC29A3 gene, encoding the human equilibrative nucleoside transporter (hENT3), characterized by cutaneous hyperpigmentation and hypertrichosis, hepatosplenomegaly, hearing loss, heart anomalies, hypogonadism, low height, hyperglycemia/insulin-dependent diabetes mellitus, and hallux valgus/flexion contractures. Exophthalmos, malabsorption, renal anomalies, flexion contractions of interphalangeal joints and hallux valgus, and lytic bone lesions, as well as osteosclerosis, are also seen. If these are lacking, the constellation of additional findings should raise suspicion for H syndrome. As most of the patients reported to date with H syndrome are from traditional, low-income populations, where consanguinity is common, it is highly important to develop a cheap and affordable technique for a mutation analysis. Two siblings presented to us, diagnosed as having insulin-dependent diabetes mellitus (IDDM) since the age of eight years and progressive flexion contracture of the small joints for seven-eight years. On examination, both had short stature. One also had bilateral cervical lymphadenopathy. The female had the Tanner stage of B3P3A2 M0 and the male had the Tanner stage of prepuberty. Laboratory workup, including antinuclear antibodies, rheumatoid factor, erythrocyte sedimentation rate, thyroid profile, and Celiac serology were negative. Genetic studies confirmed the diagnosis of H syndrome

New Pyrimidinone Bearing Aminomethylenes and Schiff Bases as Potent Antioxidant, Antibacterial, SARS-CoV-2, and COVID-19 Main Protease M Pro Inhibitors: Design, Synthesis, Bioactivities, and Computational Studies

New 2-thioxopyrimidinone derivatives (A1–A10) were synthesized in 87–96% yields via a simple three-component condensation reaction. These compounds were screened extensively through in vitro assays for antioxidant and antibacterial investigations. The DPPH assays resulted in the excellent potency of A6–A10 as antioxidants with IC50 values of 0.83 ± 0.125, 0.90 ± 0.77, 0.36 ± 0.063, 1.4 ± 0.07, and 1.18 ± 0.06 mg/mL, which were much better than 1.79 ± 0.045 mg/mL for the reference ascorbic acid. These compounds exhibited better antibacterial potency against Klebsiella with IC50 values of 2 ± 7, 1.32 ± 8.9, 1.19 ± 11, 1.1 ± 12, and 1.16 ± 11 mg/mL for A6–A10. High-throughput screenings (HTS) of these motifs were carried out including investigation of drug-like behaviors, physiochemical property evaluation, and structure-related studies involving DFT and metabolic transformation trends. The radical scavenging ability of the synthesized motifs was validated through molecular docking studies through ligand–protein binding against human inducible nitric oxide synthase (HINOS) PDB ID: 4NOS, and the results were promising. Furthermore, the antiviral capability of the compounds was examined by in silico studies using two viral proteins PDB ID: 6Y84 and PDB ID: 6LU7. Binding poses of ligands were discussed, and amino acids in the protein binding pockets were investigated, where the tested compounds showed much better binding affinities than the standard inhibitors, proving to be suitable leads for antiviral drug discovery. The stabilities of the molecular docked complexes in real systems were validated by molecular dynamics simulations

Design and synthesis of arylthiophene-2-Carbaldehydes via suzuki-miyaura reactions and their biological evaluation

A series of various novel 4-arylthiophene-2-carbaldehyde compounds were synthesized in moderate to excellent yields via Suzuki-Miyaura cross-coupling with different arylboronic pinacol esters/acids. The synthesized products were screened for their antibacterial, haemolytic, antiurease, and nitric oxide (NO) scavenging capabilities and interestingly, almost all products turned out to have good activities. 3-(5-Formyl-thiophene-3-yl)-5-(trifloromethyl)benzonitrile (2d) revealed excellent antibacterial activity, showing an IC50 value of 29.7 µg/mL against Pseudomonas aeruginosa, compared to the standard drug streptomycin with an IC50 value 35.2 µg/mL and was also found to be the best NO scavenger, with an IC50 value of 45.6 µg/mL. Moreover, 4-(3-chloro-4-fluoro-phenyl)thiophene-2-carbaldehyde (2i) exhibited a superior haemolytic action and an outstanding urease inhibition, showing an IC50 value of 27.1 µg/mL

Harnessing Desert Flora: Biogenic Silver Nanoparticles from Desert Plants Combat Bacterial Infections and Biofilm Formation

In this study, we harnessed the properties of desert plants to synthesize silver nanoparticles to explore potential antimicrobial solutions. Chrozophora plicata and Heliotropium curassavicum extracts were used as green reducing agents to transform silver ions into nanoparticles. Our findings revealed novel properties of C. plicata, which have not been reported before. Surface plasmon resonance peak at 453.6 and 431 nm for C. plicata and H. curassavicum, respectively, via ultraviolet (UV) spectral analysis evidenced the successful fabrication of silver nanoparticles with particle sizes ranging from 4.3–8 and 3.1–6.97 nm respectively, which was validated by field emission scanning electron microscopy (FE-SEM). X-ray diffraction analysis revealed that the crystal structure of these nanoparticles had a face-centered cubic geometry. Fourier transform infrared spectrometry of the plant extract showed strong signals corresponding to carbohydrates, proteins, and phenolics. Antibacterial assays of the silver nanoparticles from C. plicata displayed zones of inhibition at 5 and 4 mm against Staphylococcus aureus and Escherichia coli, respectively. Meanwhile, the silver nanoparticles from H. curassavicum exhibited zones of inhibition against both pathogens at 10 and 7 mm, respectively. The test samples were substantial inhibitors of S. aureus and E. coli biofilm formation since these displayed IC50 values in the range of 8.88–10.57 mg/mL, which is as potent as the reference ciprofloxacin. Consequently, the silver nanoparticles derived from these desert plants can be potential drug candidates for treating respiratory and digestive tract infections alone or in combination with existing antibiotics

Distance and Engagement: Hegel’s Account of Critical Reflection

Hegel famously argues that Kant’s account of critical distance depends upon an impoverished conception of freedom. In its place, Hegel introduces a richer conception of freedom, according to which the self who is capable of self-determination is multifaceted: wanting and thinking, social and individual. This richer conception gives rise to an account of critical reflection that emphasizes engagement with our motives and practices rather than radical detachment from them. But what is most distinctive about Hegel’s account is the idea that when we reflect upon motives and practices, we draw upon shared self-understandings that are neither universal nor just particular to individuals. There is, Hegel argues, no presocial identity or self that can be detached from our socially constituted contexts of thought and value. This has important implications for how we conceive of critical reflection

Efficient synthesis of 2-amino-6-arylbenzothiazoles via Pd(0) Suzuki cross coupling reactions : potent urease enzyme inhibition and nitric oxide scavenging activities of the products

In general, benzothiazole derivatives have attracted great interest due to thier pharmaceutical and biological importance. New 2-amino-6-arylbenzothiazoles were synthesized in moderate to excellent yields via Suzuki cross coupling reactions using various aryl boronic acids and aryl boronic acid pinacol esters and the antiurease and nitric oxide (NO) scavenging activity of the products were also examined. The most active compound concerning urease enzyme inhibition was 6-phenylbenzo[d]thiazole-2-amine 3e, with an IC50 value of 26.35 µg/mL. Compound 3c, 6-(4-methoxyphenyl) benzo[d]thiazole-2-amine, exhibited the highest nitric oxide percentage scavenging at 100µg/mL

Role of nanotechnology for design and development of cosmeceutical: Application in makeup and skin care

Nanotechnology is an innovative area of science that includes the design, characterization, production, and application of materials, devices and systems by controlling shape and size at the nanometer scale (1–100 nm). Nanotechnology incorporation in cosmetic formulation is considered as the hottest and emerging technology available. Cosmetic manufacturers use nanoscale size ingredients to provide better UV protection, deeper skin penetration, long-lasting effects, increased color, finish quality, and many more. Micellar nanoparticles is one of the latest field applied in cosmetic products that becoming trending and widely commercialized in local and international markets. The ability of nanoemulsion system to form small micellar nanoparticles size with high surface area allowing to effectiveness of bioactive component transport onto the skin. Oil in water nanoemulsion is playing a major role as effective formulation in cosmetics such as make-up remover, facial cleanser, anti-aging lotion, sun-screens, and other water-based cosmetic formulations. The objective of this review is to critically discuss the properties, advantageous, and mechanism of micellar nanoparticles formation in nanoemulsion system. Therefore, present article introduce and discuss the specific benefits of nanoemulsion system in forming micellar nanoparticles for cosmetic formulation which become major factors for further development of micellar-based cosmetic segments

A convenient method for the synthesis of (prop-2-ynyloxy)benzene derivatives via reaction with propargyl bromide, their optimization, scope and biological evaluation

A highly convenient method has been developed for the synthesis of (prop-2-ynyloxy) benzene and its derivatives. Differently substituted phenol and aniline derivatives were allowed to react with propargyl bromide in the presence of K2CO3 base and acetone as solvent. The compounds were synthesized in good yields (53–85%). Low cost, high yields and easy availability of compounds helped in the synthesis. Electron withdrawing groups favor the formation of stable phenoxide ion thus in turn favors the formation of product while electron donating groups do not favor the reaction. Phenol derivatives gave good yields as compared to that of aniline. As aprotic polar solvents favor SN2 type reactions so acetone provided best solvation for the reactions. K2CO3 was proved to be good for the synthesis. Antibacterial, Antiurease and NO scavenging activity of synthesized compounds were also examined. 4-bromo-2-chloro-1-(prop-2-ynyloxy)benze​ne2a was found most active compound against urease enzyme with a percentage inhibition of 82.00±0.09 at 100 µg/mL with IC50 value of 60.2. 2-bromo-4-methyl-1-(prop-2-ynyloxy)benze​ne2d was found potent antibacterial against Bacillus subtillus showing excellent inhibitory action with percentage inhibition of 55.67±0.26 at 100 µg/ml wih IC50 value of 79.9. Based on results, it can be concluded that some of the synthesized compounds may have potential antiurease and antibacterial effects against several harmful substances