Recent advances in environmental and agricultural applications of hydrochars: A review.

Hydrochar is a carbonaceous material that is generated through the process of hydrothermal carbonization (HTC) from biomass, which has garnered considerable attention in recent years owing to its potential applications in a diverse range of fields, such as environmental remediation and agriculture. Hydrochar is produced from a diverse range of biomass waste materials and retains exceptional properties, including high carbon content, stability, and surface area, making it an optimal candidate for various enviro-agricultural applications. Moreover, it delves into the production process of hydrochar, with explicit emphasis on the optimization of certain properties during the production of hydrochar from bio-waste. Furthermore, the potential of hydrochar as an adsorbent and catalyst support for heavy metals and dyes was extensively explored, along with a soil remediation potential that can improve the physical, chemical and biological properties of soil. This comprehensive review aims to provide a thorough overview of hydrochar with a particular focus on its production, properties, and prospective applications. The significance of hydrochar is accentuated and the growing need for alternative sources of energy and materials that are environmentally sustainable is highlighted in this paper. Besides, the consequence of hydrochar on soil properties such as water-holding capacity, nutrient retention, and total soil porosity, as well as its influence on soil chemical properties such as cation exchange capacity, electrical conductivity, and surface functionality is scrutinized.

Synthesis, anti-inflammatory activity, inverse molecular docking, and acid dissociation constants of new naphthoquinone-thiazole hybrids.

Chronic Inflammation is associated with various types of diseases that involves pro-inflammatory cytokines like IL-6 and TNF-α. High costs and serious side effects of available anti-inflammatory/immunomodulatory drugs led us to design new compounds with promising anti-inflammatory activities. Many drugs and biologically important compounds involve naphthoquinone and thiazole moieties in their core structures. Thereby, here we report the synthesis, characterization and anti-inflammatory activities of new naphthoquinone thiazole hybrids by reaction of naphthoquinone acyl thioureas with various α-bromoketone derivatives. The position of NO2 group in one of the phenyl rings of naphthoquinone thiazole hybrids was changed while different substituents were introduced at the para position of the second phenyl ring. All compounds were tested for potential immunomodulatory effect. No inflammatory cytokines were observed in the absence of LPS stimulant. On the other hand, they had promising anti-inflammatory immunomodulatory activities by being able to decrease the production of the pro-inflammatory cytokines (TNF-α and IL-6) in the LPS-stimulated cells. In an effort to find the possible mechanism of action, several enzymes involved in signalling pathways that play critical roles in inflammatory responses were screened in silico. Subsequent to inverse molecular docking approach, PI3K was predicted be the potential target. The docked complexes of the most potent compounds 5g and 5i were subjected to molecular dynamics simulation to assess the binding stability of the igands with the putative target. Acid dissociation constants (pKa) of the products were also determined potentiometrically.

Design and synthesis of silver nanoparticle anchored poly(ionic liquid)s mesoporous for controlled anticancer drug delivery with antimicrobial effect.

Owing to the importance of drug delivery, the synthesis of advanced nanomaterials for targeted drug delivery plays a considerable role in medical treatment. One of the most prominent nanomaterials is PIL, which is used as controlled anticancer drug delivery and significantly improves the half-life and antitumor effect. In this study, a stable and effective drug carrier containing silver nanoparticles was reported for the drug delivery with an antimicrobial effect, and the capability of the drug carrier . PILP was synthesized by radical polymerization, and silver nanoparticles were anchored into PIL voids by in-situ reduction, which developed the adsorption antimicrobial effect and capability of the drug carrier. The synthesized nanocomposite was characterized. The Ag-PILP nanocomposite showed antibacterial activityagainst both E. coli and S. aureus with a MIC of 256 µg/mL, and bactericidal activity against E. coli and S. aureus strains with a MBC of 256 and 512 µg/mL, respectively.

The 1,2,3-triazole 'all-in-one' ring system in drug discovery: a good bioisostere, a good pharmacophore, a good linker, and a versatile synthetic tool.

INTRODUCTION: The 1,2,3-triazole ring occupies an important space in medicinal chemistry due to its unique structural properties, synthetic versatility and pharmacological potential making it a critical scaffold. Since it is readily available through click chemistry for creating compound collections against various diseases, it has become an emerging area of interest for medicinal chemists. AREAS COVERED: This review article addresses the unique properties of the1,2,3-triazole nucleus as an intriguing ring system in drug discovery while focusing on the most recent medicinal chemistry strategies exploited for the design and development of 1,2,3-triazole analogs as inhibitors of various biological targets. EXPERT OPINION: Evidently, the 1,2,3-triazole ring with unique structural features has enormous potential in drug design against various diseases as a pharmacophore, a bioisoster or a structural platform. The most recent evidence indicates that it may be more emerging in drug molecules in near future along with an increasing understanding of its prominent roles in drug structures. The synthetic feasibility and versatility of triazole chemistry make it certainly ideal for creating compound libraries for more constructive structure-activity relationship studies. However, more comparative and target-specific studies are needed to gain a deeper understanding of the roles of the 1,2,3-triazole ring in molecular recognition.[Figure: see text].

Does anti-IgE therapy prevent chronic allergic asthma-related bone deterioration in asthmatic mice?

Current evidence on the association between allergic diseases and bone metabolism indicates asthma may be a potential risk factor for bone health. Using anti-IgE has been proven effective in allergic asthma treatment with a good safety profile; however, its effects on bone health are unknown. Thus, we aimed to investigate whether: (i) chronic allergic asthma (CAA) causes any meaningful changes in bone, and if any, (ii) anti-IgE therapy prevents any CAA-induced adverse alteration. A murine model was used to study CAA. Thirty-two BALB/c male-mice were assigned into four groups (eight-mice/group): Control, CAA (treated with saline), CAA + 100 µg of anti-IgE (CAA + 100AIgE), and CAA + 200 µg of anti-IgE (CAA + 200AIgE) groups. After immunization, saline or anti-IgE was performed intraperitoneally for 8-weeks (in five-sessions at 15-days interval). Three-point bending test was used for the mechanical analysis. Bone calcium (Ca2+) and phosphorus (P3-) as well as Ca/P ratio were evaluated using inductively-coupled plasma-mass-spectrometer (ICP-MS). Compared to control, reductions observed in yield and ultimate moments, rigidity, energy-to-failure, yield and ultimate stresses, elastic modulus, toughness, and post-yield toughness parameters of the CAA group were found significant (P < 0.05). Similar declines were also detected regarding bone Ca2+, P3- and Ca/P ratio (P < 0.05). Compared to control, we observed that 200 µg administration of anti-IgE in CAA + 200AIgE group hindered CAA-related impairments in mineral and mechanical characteristics of bone, while 100 µg in CAA + 100AIgE failed to do so. Our results showed CAA may cause bone loss, leading to a decrease in bone strength, and anti-IgE administration may dose-dependently inhibit these impairments in bone.

Synthesis of novel immunomodulatory 1,4-disubstituted bis-1,2,3-triazoles by using click chemistry and their intracellular mechanism of action.

In this study, six new 1,4-disubstituted bis-1,2,3-triazole compounds, N,N'-(1,2-phenylene)bis(2-(4-R-1H-1,2,3-triazol-1-yl)acetamide), were synthesized with high yield (88-96 %) by using click chemistry and their molecular structures were characterized by using NMR, FT-IR, HRMS and elemental analysis techniques. Previous studies suggest anti-inflammatory and analgesic activities for different 1,2,3-triazole derivatives and in the light of those studies we aimed to examine these novel derivatives immunomodulatory activities on the mammalian macrophages. Pro-inflammatory cytokines (TNF, IL6, GMCSF and IL12p40) secretion levels were tested in the presence of bis-1,2,3-triazole compounds when the macrophages were activated with LPS. These new derivatives were able to suppress the production of these cytokines at different levels. Intracellular phophorylated PI3K protein levels were measured due to its prominent role in inflammatory reactions. Our flow cytometry analysis results suggested that some of these compounds were partially effective through PI3K pathway. In different inflammatory and autoimmune disease settings these novel 1,2,3-triazole derivatives can be utilized as non-steroid based anti-inflammatory drug candidates.

A Review on the Design, Synthesis, and Structure-activity Relationships of Benzothiazole Derivatives against Hypoxic Tumors.

There has been a growing body of studies on benzothiazoles and benzothiazole derivatives as strong and effective anti-tumor agents against lung, liver, pancreas, breast, and brain tumors. Due to the highly proliferative nature of the tumor cells, the oxygen levels get lower than that of normal tissues in the tumor microenvironment. This situation is called hypoxia and has been associated with increased ability for carcinogenesis. For the drug design and development strategies, the hypoxic nature of the tumor tissues has been exploited more aggressively. Hypoxia itself acts as a signal initiating system to activate the pathways that eventually lead to the spread of the tumor cells into the different tissues, increases the rate of DNA damage, and eventually ends up with more mutation levels that may increase the drug resistance. As one of the major mediators of hypoxic response, hypoxia-inducible factors (HIFs) have been shown to activate angiogenesis, metastasis, apoptosis resistance, and many other protumorigenic responses in cancer development. In the current review, we will be discussing the design, synthesis, and structureactivity relationships of benzothiazole derivatives against hypoxic tumors such as lung, liver, pancreas, breast, and brain as potential anti-cancer drug candidates. The focus points of the study will be the biology behind carcinogenesis and how hypoxia contributes to the process, recent studies on benzothiazole and its derivatives as anti-cancer agents against hypoxic cancers, conclusions, and future perspectives. We believe that this review will be useful for researchers in the field of drug design during their studies to generate novel benzothiazole-containing hybrids against hypoxic tumors with higher efficacies.

New bis- and tetrakis-1,2,3-triazole derivatives: Synthesis, DNA cleavage, molecular docking, antimicrobial, antioxidant activity and acid dissociation constants.

In this study, a series of bis- and tetrakis-1,2,3-triazole derivatives were synthesized using copper-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry in 73-95% yield. The bis- and tetrakis-1,2,3-triazoles exhibited significant DNA cleavage activity while the tetrakis-1,2,3-triazole analog 6g completely degraded the plasmid DNA. Molecular docking simulations suggest that compound 6g acts as minor groove binder of DNA by binding through several noncovalent interactions with base pairs. All bis- and tetrakis-1,2,3-triazole derivatives were screened for antibacterial activity against E. coli, B. cereus, S. aureus, P. aeruginosa, E. hirae, L. pneumophila subsp. pneumophila strains and antifungal activity against microfungus C. albicans and C. tropicalis strains. Compound 4d exhibited the best antibacterial activity among bis-1,2,3-triazoles against E. coli and E. hirae, while 6c exhibited the best antibacterial activity among tetrakis-1,2,3-triazoles against E. hirae. Furthermore, the best antifungal activity against C. albicans and C. tropicalis was reported for the compound 5, while 6d displayed the best antifungal activity against C. tropicalis and C. albicans. Reasonable iron chelating activities and DPPH radical scavenging abilities were found for some of the compounds. Finally, the acid dissociation constants (pKa) of the bis-1,2,3-triazoles were also determined with the help of HYPERQUAD program using the data obtained from potentiometric titrations. The reported data here concludes that the bis- and tetrakis-1,2,3-triazoles are important cores that should be considered for further development of especially new anticancer agents acting through the DNA cleavage activity.

Synthesis, biological properties, and acid dissociation constant of novel naphthoquinone-triazole hybrids.

A series of novel 1,4-naphthoquinone-triazole hybrids, N-(3-amino-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-2-(4-R-1H-1,2,3-triazol-1-yl)acetamide, was synthesized by click chemistry in the presence of sodium ascorbate and copper(II) sulfate pentahydrate in 81-94% yield. Various biological properties of the synthesized compounds including DNA binding/cleavage, antioxidant, antibacterial and antifungal properties were evaluated. The DNA binding study was performed using dsDNA and G-quadruplex DNA. All of the compounds showed fluorescence increase in the presence of DNA, regardless of the structure. Up to 2.9 and 2.5 times fluorescence increase upon incubation with double stranded or G-quadruplex DNA was detected for 5f and 5g, respectively. The docking studies performed on dsDNA and G-quadruplex structures suggested compounds' mode of interactions were populated around the grooves. All of the compounds showed excellent DNA cleavage activity and 5e was almost degraded the plasmid DNA. The highest radical scavenging activity was obtained as 89.9% at 200 mg/L with 5d. However, the highest ferrous chelating activity was obtained as 68.1% at 200 mg/L with 5g. The compounds exhibited antimicrobial activity against Bacillus cereus, Legionella pneumophila subsp. pneumophila, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Enterococcus hirae as bacteria strains and Candida albicans and Candida tropicalis as microfungus strains. The compounds exhibited antibacterial and antifungal activity in the range of 4-128 µg/mL and 16-128 µg/mL, respectively. The best antimicrobial activity was obtained with 5d and 5e with a MIC value of 4 µg/mL against Enterococcus hirae. The acid dissociation constants (pKa) were determined potentiometrically in 20% (v/v) dimethyl sulfoxide-water hydro-organic solvent at an ionic background of 0.1 mol/L of NaCl, at 25 ± 0.1 °C. Five pKa values were obtained for each ligand.

Synthesis, antimicrobial activity and acid dissociation constants of methyl 5,5-diphenyl-1-(thiazol-2-yl)pyrrolidine-2-carboxylate derivatives.

In this study, a series of polysubstituted methyl 5,5-diphenyl-1-(thiazol-2-yl)pyrrolidine-2-carboxylate derivatives were designed and synthesized by the cyclization reaction of methyl 1-(benzoylcarbamothioyl)-5,5-diphenylpyrrolidine-2-carboxylates and 2-bromo-1-(4-substituted phenyl)ethanones in 70-96% yield. The starting pyrrolidine derivatives were synthesized via a 1,3-dipolar cycloaddition reaction in 83-88% yield. The stereochemistry of one of these methyl 5,5-diphenyl-1-(thiazol-2-yl)pyrrolidine-2-carboxylate derivatives was characterized by a single crystal X-ray diffraction study and the acid dissociation constants of these compounds were determined. An antimicrobial screening was performed against different bacterial and fungal strains and against the M. tuberculosis H37Rv strain. Interesting antibacterial activity was observed for two compounds against the A. baumannii strain with MIC values of 31.25 µg/mL (Ampicillin: 125 µg/mL) and against the M. tuberculosis H37Rv strain with MIC values of 0.98-1.96 µg/mL (Isoniazid: 0.98 µg/mL, Ethambutol: 1.96 µg/mL). Therefore, these structures can be considered as good starting points for the development of new powerful antimycobacterial agents.

Determination of Acid Dissociation Constants (pK a ) of Bicyclic Thiohydantoin-Pyrrolidine Compounds in 20% Ethanol-Water Hydroorganic Solvent.

The acid dissociation constants of potential bioactive fused ring thiohydantoin-pyrrolidine compounds were determined by potentiometric titration in 20% (v/v) ethanol-water mixed at 25 ± 0.1°C, at an ionic background of 0.1 mol/L of NaCl using the HYPERQUAD computer program. Proton affinities of potential donor atoms of the ligands were calculated by AM1 and PM3 semiempiric methods. We found, potentiometrically, three different acid dissociation constants for 1a-f. We suggest that these acid dissociation constants are related to the carboxyl, enol, and amino groups.