Structure, chemical modification, and functional applications of mucilage from Mimosa pudica seeds - A review.

Mimosa pudica (MP) is an ornamental plant due to seismonastic movements that close leaves and fall petioles in response to touch, wind, light, heat, cold, and vibration. The seeds of MP secrete smart, biocompatible, and non-toxic mucilage that has captivated researchers due to its widespread use in various fields such as pharmaceuticals and biotechnology. The mucilage is responsive to pH, salt solutions, and solvents and acts as a binder in tablet formulations for targeted drug delivery. The mucilage is chemically modifiable via acetylation, succinylation, and graft polymerization. Chemically modified MP mucilage appeared supersorbent for heavy metal ion uptake. Nanoparticles synthesized using mucilage as a reducing and capping agent displayed significant antimicrobial and wound-healing potential. Crosslinking of mucilage using citric acid as a crosslinking agent offers a sustained release of drugs. The present review is aimed to discuss extraction optimization, structure, modification, and the stimuli-responsive nature of mucilage. The review article will cover the potential of mucilage as emulsifying, suspending, bio-adhesive, gelling, and thickening agent. The role of mucilage as a capping and reducing agent for nanoparticles will also be discussed.

Correction: Abbas et al. Bioactive Compounds, Antioxidant, Anti-Inflammatory, Anti-Cancer, and Toxicity Assessment of Tribulus terrestris-In Vitro and In Vivo Studies. Antioxidants 2022, 11, 1160.

In the original publication [...].

Pharmacological and Therapeutic Potential of Berbamine: A Potent Alkaloid from Genus Berberis.

Berbamine (Ber) is an active medicinal bisbenzylisoquinoline alkaloid, which is usually obtained from different plants of the genus Berberis (family Berberidaceae) and is used to cure various disorders in traditional Chinese and Ayurvedic systems of medicine. Numerous in-vitro and in-vivo studies revealed the apoptotic and cytotoxic potential of Ber against different cell lines (SMMC-7721, A549, MDA-MB-231, and K562) by upregulating pro-apoptotic (Bax, p53) and downregulating anti-apoptotic (Bcl-2, survivin) proteins. Other pharmacological attributes ascribed to Ber included cardioprotective, anti-diabetic, anti-inflammatory, antimalarial, antioxidant, anti-hypercholesterolemic, and anti-allergic. Moreover, the synergistic effect of Ber improved the therapeutic potential of different drugs (paclitaxel (PTL), gemcitabine, dexamethasone, doxorubicin (DOX), and celecoxib) in different models. Various attempts could fabricate biologically active derivatives of Ber, such as 4-chlorobenzoyl berbamine (CBB) and O-4- ethoxyl-butyl-berbamine (EBB). The review focuses on the medicinal applications of Ber, particularly anti-cancer, cardioprotective, and anti-inflammatory, along with the mechanism of action.

Synthesis of the chromone-thiosemicarbazone scaffold as promising α-glucosidase inhibitors: An in vitro and in silico approach toward antidiabetic drug design.

Diabetes is a serious metabolic disorder affecting individuals of all age groups and prevails globally due to the failure of previous treatments. This study aims to address the most prevalent form of type 2 diabetes mellitus (T2DM) by reporting on the design, synthesis, and in vitro as well as in silico evaluation of chromone-based thiosemicarbazones as potential α-glucosidase inhibitors. In vitro experiments showed that the tested compounds were significantly more potent than the standard acarbose, with the lead compound 3n exhibiting an IC50 value of 0.40 ± 0.02 µM, ~2183-fold higher than acarbose having an IC50 of 873.34 ± 1.67 µM. A kinetic mechanism analysis demonstrated that compound 3n exhibited reversible inhibition of α-glucosidase. To gain deeper insights, in silico molecular docking, pharmacokinetics, and molecular dynamics simulations were conducted for the investigation of the interactions, orientation, stability, and conformation of the synthesized compounds within the active pocket of α-glucosidase.

Synthesis, in vitro, and in silico studies of morpholine-based thiosemicarbazones as ectonucleotide pyrophosphatase/phosphodiesterase-1 and -3 inhibitors.

An extensive range of new biologically active morpholine based thiosemicarbazones derivatives 3a-r were synthesized, characterized by spectral techniques and evaluated as inhibitors of ENPP isozymes. Most of the novel thiosemicarbazones exhibit potent inhibition towards NPP1 and NPP3 isozymes. Compound 3 h was potent inhibitor of NPP1 with IC50 value of 0.55 ±â€¯0.02. However, the most powerful inhibitor of NPP3 was 3e with an IC50 value of 0.24 ±â€¯0.02. Furthermore, Lineweaver-Burk plot for compound 3 h against NPP1 and for compound 3e against NPP3 was devised through enzymes kinetics studies. Molecular docking and in silico studies was also done for analysis of interaction pattern of all newly synthesized compounds. The results were further validated by molecular dynamic (MD) simulation where the stability of conformational transformation of the best protein-ligand complex (3e) were justified on the basis of RMSD and RMSF analysis.

Synthesis, characterization and NLO properties of 1,4-phenylenediamine-based Schiff bases: a combined theoretical and experimental approach.

In the current study, three novel 1,4-phenylenediamine-based chromophores (3a-3c) were synthesized and characterized and then their nonlinear optical (NLO) characteristics were explored theoretically. The characterization was done by spectroscopic analysis, i.e. FT-IR, UV-Visible, and NMR spectroscopy, and elemental analysis. Notably, these chromophores exhibited UV-Visible absorption within the range of 378.635-384.757 nm in acetonitrile solvent. Additionally, the FMO findings for 3a-3c revealed the narrowest band gap (4.129 eV) for 3c. The GRPs for these chromophores were derived from HOMO-LUMO energy values, which showed correspondence with FMO results by depicting a minimum hardness (2.065 eV) for 3c. Among these compounds, 3c displayed the highest nonlinear behavior with maximum µtot, ßtot and γtot values of 4.79 D, 8.00 × 10-30 and 8.13 × 10-34 a.u., respectively. Our findings disclosed that the synthesized 1,4-phenylenediamine chromophores may be considered promising candidates for nonlinear optical materials, showing potential applications in the realm of optoelectronic devices.

Synthesis of 3-hydroxy-2-naphthohydrazide-based hydrazones and their implications in diabetic management via in vitro and in silico approaches.

Diabetes mellitus (DM) has prevailed as a chronic health condition and has become a serious global health issue due to its numerous consequences and high prevalence. We have synthesized a series of hydrazone derivatives and tested their antidiabetic potential by inhibiting the essential carbohydrate catabolic enzyme, "α-glucosidase." Several approaches including fourier transform infrared, 1 H NMR, and 13 C NMR were utilized to confirm the structures of all the synthesized derivatives. In vitro analysis of compounds 3a-3p displayed more effective inhibitory activities against α-glucosidase with IC50 in a range of 2.80-29.66 µM as compared with the commercially available inhibitor, acarbose (IC50 = 873.34 ± 1.67 M). Compound 3h showed the highest inhibitory potential with an IC50 value of 2.80 ± 0.03 µM, followed by 3i (IC50 = 4.13 ± 0.06 µM), 3f (IC50 = 5.18 ± 0.10 µM), 3c (IC50 = 5.42 ± 0.11 µM), 3g (IC50 = 6.17 ± 0.15 µM), 3d (IC50 = 6.76 ± 0.20 µM), 3a (IC50 = 9.59 ± 0.14 µM), and 3n (IC50 = 10.01 ± 0.42 µM). Kinetics analysis of the most potent compound 3h revealed a concentration-dependent form of inhibition by 3h with Ki value = 4.76 ± 0.0068 µM. Additionally, an in silico docking approach was applied to predict the binding patterns of all the compounds, which indicates that the hydrazide and the naphthalene-ol groups play a vital role in the binding of the compounds with the essential residues (i.e., Glu277 and Gln279) of the α-glucosidase enzyme.

Design, synthesis, molecular docking and biological evaluation of 1,3,5-trisubstituted-1H-pyrazole derivatives as anticancer agents with cell cycle arrest, ERK and RIPK3- kinase activities.

The need for new ERK and RIPK3 kinase modulators arises from their central roles in cellular processes, especially in diseases like cancer. This research focused on a ligand-based strategy, incorporating previously documented 1,3,5-trisubstituted-1H-pyrazole derivatives, to craft innovative inhibitors specifically targeting ERK and RIPK3 kinases. Compounds 6, 7, 10a, 10c, and 10d exhibited significant cytotoxicity against PC-3 and MCF-7 cancer cell lines, with IC50 values ranging from 21.9 to 28.6 µM and 3.90-35.5 µM, respectively values surpassing those of the reference compound Doxorubicin. Additionally, cell cycle analysis revealed intriguing results, particularly with 10d inducing cell cycle arrest at the S phase in treated PC-3 cells, indicating potential DNA replication phase inhibition. Moreover, compounds 6, 10a, and 10d exhibited promising results in the in vitro kinase assay supported by molecular docking studies. The core scaffold of these compounds established interactions with vital amino acids within the active pockets of ERK and RIPK3 kinases, thereby securely anchoring them in place. These findings underscore the development of promising modulators for ERK and RIPK3 kinases, suggesting their potential for future contributions to cancer treatments.

Carbonylbis(hydrazine-1-carbothioamide) derivatives as a new class of α-glucosidase inhibitors and their mechanistic insights via molecular docking and dynamic simulations.

In the past, efforts have been made to find a cure for diabetes, mainly evaluating new classes of compounds to explore their potency. In this study, we present the synthesis and evaluation of carbonylbis(hydrazine-1-carbothioamide) derivatives as potential α-glucosidase inhibitors, employing both in vivo and in silico investigations. The in vitro experiments revealed that all tested compounds were significantly potent for α-glucosidase inhibition, with the lead compound 3a displaying approximately 80 times higher activity than acarbose. To delve deeper, in silico induced fit docking, pharmacokinetics, and molecular dynamics studies were conducted. Significantly, compound 3a exhibited a docking score of -7.87 kcal/mol, surpassing acarbose, which had a docking score of -6.59 kcal/mol. The in silico ADMET indicated that most of the synthesized compounds have properties conducive to drug development. Molecular dynamics analysis demonstrated that, when the ligand 3a was coupled with the target 3TOP, Cα-RMSD backbone RMSD values below 2.4 Å and "Lig_fit_Prot" values below 2.7 Å were observed. QSAR analysis demonstrates that the "fOC8A" descriptor positively correlates with α-glucosidase inhibition activity, while "lipoplus_AbSA" positively contributes and "notringC_notringO_8B" negatively contributes to this activity.

Synthesis, biological evaluation, and molecular docking study of xanthene-linked thiosemicarbazones as cholinesterase inhibitors.

This study delineates the design and synthesis of a series of xanthene-based thiosemicarbazones that show low µM inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), crucial enzymes associated with, among others, Alzheimer's Disease (AD) pathology. Despite FDA-approved AChE inhibitors being frontline treatments for AD, there remains a need for agents exhibiting improved efficacy and selectivity. Our synthesized series demonstrate meaningful inhibition against AChE (IC50 ranging from 4.2 to 62 µM). These compounds exhibit comparatively lower potency against BChE (IC50 values between 64 and 315 µM), showcasing a pronounced AChE selectivity compared to physostigmine. The selectivity index for the compounds between the two targets does vary between 0.02 and 0.75 highlighting that even minor structural differences can have drastic effects on protein interactions. Molecular docking insights further substantiated these observations, revealing the importance of the xanthene scaffold for AChE-binding and the aryl R2 moiety for BChE interactions. Notably, some compounds demonstrated dual enzyme targeting, emphasizing their interactions could be exploited for developing monotherapies against cholinesterase-associated neurodegenerative afflictions like AD. Collectively, these findings suggest that xanthene-based thiosemicarbazones are a promising and highly accessible scaffold that deserve further investigative exploration in the cholinesterase inhibitor therapeutic landscape.Communicated by Ramaswamy H. Sarma.

Multicomponent synthesis of pyrido[2,3-b]pyrazine derivatives: electrochemical DNA sensing, nonlinear optical properties and biological activity.

We synthesized novel pyrido[2,3-b]pyrazin based heterocyclic compounds (4-7) and their chemical structures were ascertained by spectral techniques (NMR, FT-IR). Besides experimental investigation, density functional theory (DFT) computations with B3LYP/6-31G(d,p) level of theory were executed to obtain spectroscopic and electronic properties. Nonlinear optical (NLO) properties, frontier molecular orbitals (FMOs), UV-visible, vibrational analysis, natural bond orbitals (NBOs), transition density matrix (TDM) and density of states (DOS) analyses of molecules (4-7) were accomplished at B3LYP/6-31G (d,p) level. Global reactivity parameters (GRPs) were correlated with the band gap (Egap) values; compound 7 with lower Egap (3.444 eV), exhibited smaller value of hardness (1.722 eV) with greater softness value (0.290 eV-1). The dipole moment (µ), average polarizability 〈α〉, first (ßtot) and second 〈γ〉 hyper-polarizabilities were calculated for compounds (4-7). Compound 7 showed less Egap, highest absorption wavelength and remarkable NLO response. The highest 〈α〉, ßtot and 〈γ〉 values for compound 7 were observed as 3.90 × 10-23, 15.6 × 10-30 and 6.63 × 10-35 esu, respectively. High NLO response revealed that pyrido[2,3-b]pyrazin based heterocyclic compounds had very remarkable contributions towards NLO technological applications. Further compounds (4-7) are utilized for the first time in electrochemical sensing of DNA, in vitro antioxidant and antiurease activity.

Synthesis of novel coumarin-based thiosemicarbazones and their implications in diabetic management via in-vitro and in-silico approaches.

Diabetes mellitus has a high prevalence rate and it has been deemed a severe chronic metabolic disorder with long-term complications. This research aimed to identify compounds that could potentially inhibit the vital metabolic enzyme α-glucosidase and thereby exert an anti-hyperglycemic effect. The main goal was to establish an effective approach to control diabetes. To proceed with this study, a series of novel coumarin-derived thiosemicarbazones 3a-3m was synthesized and examined using a variety of spectroscopic methods. Moreover, all the compounds were subjected to α-glucosidase inhibition bioassay to evaluate their antidiabetic potential. Fortunately, all the compounds exhibited several folds potent α-glucosidase inhibitory activities with IC50 values ranging from 2.33 to 22.11 µM, in comparison to the standard drug acarbose (IC50 = 873.34 ± 1.67 µM). The kinetic studies of compound 3c displayed concentration-dependent inhibition. Furthermore, the binding modes of these molecules were elucidated through a molecular docking strategy which depicted that the thiosemicarbazide moiety of these molecules plays a significant role in the interaction with different residues of the α-glucosidase enzyme. However, their conformational difference is responsible for their varied inhibitory potential. The molecular dynamics simulations suggested that the top-ranked compounds (3c, 3g and 3i) have a substantial effect on the protein dynamics which alter the protein function and have stable attachment in the protein active pocket. The findings suggest that these molecules have the potential to be investigated further as novel antidiabetic medications.

2-Oxoquinoline-based-thiosemicarbazones as multitargeting neurotherapeutics against Alzheimer's disease: In vitro and in silico studies of MAO and ChE inhibitors.

Alzheimer's disease (AD) presents a multifactorial neurological disorder with multiple enzyme involvement in its onset. Conventional monotherapies fall short in providing long-term relief, necessitating the exploration of alternative multitargeting approaches to address the complexity of AD. Therefore, the design, synthesis, and in vitro and in silico evaluation of 2-oxoquinoline-based thiosemicarbazones 9a-r as multipotent analogs, able to simultaneously inhibit the cholinesterase (ChE) and monoamine oxidase (MAO) enzymes for the potential treatment of AD, are reported. In the in vitro experimental evaluation of MAO and ChE inhibition, all tested compounds demonstrated remarkable potency exhibiting nonselective inhibition of both MAO-A and MAO-B, and selective inhibition of acetylcholinesterase (AChE) over butyrylcholinesterase (BChE), with 9d, 9j, and 9m evolving as lead compounds for MAO-A, MAO-B, and AChE, displaying IC50 values of 0.35 ± 0.92, 0.50 ± 0.02, and 0.25 ± 0.13 µM, respectively. Moreover, the kinetic studies revealed that all tested compounds inhibited all three enzymes through a competitive mode of inhibition. Furthermore, the molecular docking studies of the most active compounds revealed several crucial interactions, particularly hydrogen bonding interactions. These interactions were observed between the nitrogen and sulfur atoms of thiosemicarbazone and the nitrogen and oxygen atoms of the quinoline ring with various amino acids, suggesting the strong interactions of these compounds with the enzymes.

Correction: Recent trends in ozone sensing technology.

Correction for 'Recent trends in ozone sensing technology' by Muhammad Mudassir Iqbal et al., Anal. Methods, 2023, 15, 2798-2822, https://doi.org/10.1039/D3AY00334E.

Synthesis, biological evaluation and molecular modelling of 3-Formyl-6-isopropylchromone derived thiosemicarbazones as α-glucosidase inhibitors.

Type-2 Diabetes Mellitus (T2DM) is one of the most common metabolic disorders in the world and over the past three decades its incidence has increased drastically. α-Glucosidase inhibitors are used to control the hyperglycemic affect of T2DM. Herein, we report the synthesis, α-glucosidase inhibition, structure activity relationship, pharmacokinetics and docking analysis of various novel chromone based thiosemicarbazones 3(a-r). The derivatives displayed potent activity against α-glucosidase with IC50 in range of 0.11 ± 0.01-79.37 ± 0.71 µM. Among all the synthesized compounds, 3a (IC50 = 0.17 ± 0.026 µM), 3 g (IC50 = 0.11 ± 0.01 µM), 3n (IC50 = 0.55 ± 0.02 µM), and 3p (IC50 = 0.43 ± 0.025 µM) displayed higher inhibitory activity as compared to the standard, acarbose. Moreover, we have developed a statistically significant 2D-QSAR model (R2tr:0.9693; F: 50.4647 and Q2LOO:0.9190), which can be used in future to further design potent thiosemicarbazones as inhibitors of α-glucosidase.

Recent trends in ozone sensing technology.

The harmful impact of ozone on humans and the environment makes the development of economical, accurate, and efficient ozone monitoring technologies necessary. Therefore, in the present review, we critically discuss developments in the methods for the synthesis of ozone sensing materials such as metal oxides (Ni, Co, Pd, In, Cu, Zn, Fe, Sn, W, Ti and Mo), carbon nanotubes, organic compounds, perovskites, and quartz. Additionally, the recent advancements and innovations in ozone technology will be discussed. In this review, we focus on assembling ozone-sensing devices and developing related wireless communication, data transferring, and analyzing technologies together with satellite, airborne, and ground-based novel ozone-sensing strategies for monitoring the atmosphere, urban areas, and working environments. Furthermore, the developments in ozone-monitoring miniaturized devices technology will be considered. The effects of different factors, such as spatial-temporal variation, humidity, and calibration, on ozone measurements will also be discussed. It is anticipated that this review will bridge the knowledge gaps among materials chemists, engineers, and industry.

Therapeutic potential of 1,3,4-oxadiazoles as potential lead compounds for the treatment of Alzheimer's disease.

Monoamine oxidase and cholinesterase enzymes are important targets for the treatment of several neurological diseases especially depression, Parkinson disease and Alzheimer's. Here, we report the synthesis and testing of new 1,3,4-oxadiazole derivatives as novel inhibitors of monoamine oxidase enzymes (MAO-A and MAO-B) and cholinesterase enzymes (acetyl and butyryl cholinesterase (AChE, BChE). Compounds 4c, 4d, 4e, 4g, 4j, 4k, 4m, 4n displayed promising inhibitory effects on MAO-A (IC50: 0.11-3.46 µM), MAO-B (IC50: 0.80-3.08 µM) and AChE (IC50: 0.83-2.67 µM). Interestingly, compounds 4d, 4e and 4g are multitargeting MAO-A/B and AChE inhibitors. Also, Compound 4m displayed promising MAO-A inhibition with IC50 of 0.11 µM and high selectivity (∼25-fold) over MAO-B and AChE enzymes. These newly synthesized analogues represent promising hits for the development of promising lead compounds for neurological disease treatment.

Synthesis, biological evaluation, and molecular docking study of chromen-linked hydrazine carbothioamides as potent α-glucosidase inhibitors.

Inhibiting α-glucosidase is a reliable method for reducing blood sugar levels in diabetic individuals. Several novel chromen-linked hydrazine carbothioamide (3a-r) were designed and synthesized by condensation of chromone-3-carbaldehyde with a variety of substituted thiosemicarbazides. The structures of these new analogues were elucidated through various advanced spectroscopic techniques (1 H NMR, 13 C NMR, and ESI-MS). The resulted compounds were screened for α-glucosidase inhibitory potential and all the compounds (3a-r) exhibited potent inhibition of α-glucosidase with IC50 values ranging 0.29-53.70 µM. Among them compounds 3c, 3f, 3h, and 3r displayed the highest α-glucosidase inhibitor capability with IC50 values of 1.50, 1.28, 1.08, and 0.29 µM, respectively. Structure-activity relationship showed that different substituted groups are responsible for the variation in the α-glucosidase inhibition. The kinetics studies of the most active inhibitor (3r) were performed, to investigate the mode of inhibition and dissociation constants (Ki), that indicated a competitive inhibitor with Ki value of 1.47 ± 0.31 µM. Furthermore, molecular docking studies was performed to reveal the possible interactions, such as H-bonding, or π-π stacking, with the key residues of α-glucosidase. Docking analysis revealed the importance of hydrazine carbothioamide moiety of compounds in the attachment of ligands with the crucial residues of α-glucosidase. The estimated pharmacokinetic, physicochemical, and drug likeness properties of compounds 3a-r reflects that these molecules have acceptable range of these properties.

Synthesis of novel 3-hydroxy-2-naphthoic hydrazones as selective chemosensors for cyanide ions.

The development of an effective and selective chemosensor for CN- ions has become the need of the hour due to their hazardous impact on the environment and humans. Herein, we report the synthesis of two novel chemosensors, IF-1 and IF-2 based on 3-hydroxy-2-naphthohydrazide and aldehyde derivatives that have shown selective sensing of CN- ions. IF-2 exhibited exclusive binding with CN- ions that is further confirmed by the binding constant value of 4.77 × 104 M-1 with a low detection limit (8.2 µM). The chemosensory potential is attributed to deprotonation of the labile Schiff base center by CN- ions that results in a color change from colorless to yellow as visible by the naked eye. Accompanying this, a DFT study was also performed in order to find the interaction between the sensor (IF-1) and its ions (F-). A notable charge transfer from 3-hydroxy-2-naphthamide to 2,4-di-tert-butyl-6-methylphenol, was indicated by the FMO analysis. The QTAIM analysis revealed that in the complex compound, the strongest pure hydrogen-hydrogen bonding was observed between H53 and H58, indicated by a ρ value of +0.017807. Due to its selective response, IF-2 can be successfully used for making test strips for the detection of CN- ions.

Design, Synthesis, and Density Functional Theory Studies of Indole Hydrazones as Colorimetric "Naked Eye" Sensors for F Ions.

A new series of sensors SM-1 to SM-3 was designed and synthesized using indole carboxaldehydes (2a-2c) and 2,4-dinitrophenyl hydrazine. Accompanied by the synthesis, density functional theory investigation was also accomplished at the M06-2X/6-311G+(d,p) functional. A reduction in band gap (ΔE = 4.702-4.230 eV) along with a bathochromic shift (λmax = 433.223-471.584 nm) was seen in deprotonated chromophores than their neutral sensors. Further, significant charge transference from indole toward dinitrophenyl hydrazine was also examined. Global reactivity parameters also expressed the greater stability of sensors than that of their deprotonated form. SM-3 displayed high selectivity toward F ions as compared to SM-1 and SM-2, which respond to both F- and CN- ions. The electronic absorption spectrum was recorded in CH3CN. The sensor SM-3 showed high selectivity toward F- ions with a low detection limit (8.69 × 10-8), and the binding constant for SM-3 was determined as 7.7 × 105. The sensor displayed naked eye views as the color of solution changed from mustard to purple with a red shift of 96 nm. The mechanism suggests deprotonation from the NH group, which was confirmed by 1H NMR. The sensor is found to be useful for detection of F- ions in the real sample and for analytical application (test strip).