Ratiometric Sensing of Azithromycin and Sulfide Using Dual Emissive Carbon Dots: A Turn On-Off-On Approach.

A novel ratiometric fluorescence probe was developed for the determination of azithromycin (AZM) and sulfide ions based on the differential modulation of red emissive carbon dots (R-N@CDs) and blue emissive carbon dots (B-NS@CDs). The addition of sulfide anion selectively quenched the red emission of R-N@CDs while the blue emission of B-NS@CDs unaffected. Upon subsequent introduction of AZM to this R-N@CDs@sulfide system, the quenched red fluorescence was restored. Comprehensive characterization of the CDs was performed using UV-Vis, fluorescence, FTIR spectroscopy, XPS, and TEM. The proposed method exhibited excellent sensitivity and selectivity, with limits of detection of 0.33 µM for AZM and 0.21 µM for sulfide. Notably, this approach enabled direct detection of sulfide without requiring prior modulation of the CDs with metal ions, as is common in other reported methods. The ratiometric probe was successfully applied for the determination of AZM in biological fluids and sulfide in environmental water samples with high selectivity. This work presents the first fluorometric method for the detection of AZM in biological fluids.

Juglone from Walnut Produces Cardioprotective Effects against Isoproterenol-Induced Myocardial Injury in SD Rats.

Therapeutic and/or preventive interventions using phytochemical constituents for ischemic heart disease have gained considerable attention worldwide, mainly due to their antioxidant activity. This study investigated the cardioprotective effect and possible mechanism of juglone, a major constituent of the walnut tree, using an isoproterenol (ISO)-induced myocardial infarction (MI) model in rats. Rats were pretreated for five (5) days with juglone (1, 3 mg/kg, i.p) and atenolol (1 mg/kg, i.p) in separate experiments before inducing myocardial injury by administration of ISO (80 mg/kg, s.c) at an interval of 24 h for 2 consecutive days (4th and 5th day). The cardioprotective effect of juglone was confirmed through a lead II electrocardiograph (ECG), cardiac biomarkers (cTnI, CPK, CK-MB, LDH, ALT and AST) and histopathological study. The results of our present study suggest that prior administration of juglone (1 and 3 mg/kg) proved to be effective as a cardioprotective therapeutic agent in reducing the extent of myocardial damage (induced by ISO) by fortifying the myocardial cell membrane, preventing elevated T-waves, deep Q-waves in the ECG, heart to body weight ratio, infarction and also by normalizing cardiac marker enzymes (cTnI, CPK, CK-MB, LDH, ALT and AST) and histopathological changes, such as inflammation, edema and necrosis. In conclusion, this study has identified phytochemical constituents, in particular juglone, as a potential cardioprotective agent.

Production and Purification of Pectinase from Bacillus subtilis 15A-B92 and Its Biotechnological Applications.

Enzymes that degrade pectin are called pectinases. Pectinases of microbial origin are used in juice clarification as the process is cost-effective. This study screened a pectinase-producing bacterium isolated from soil and identified as Bacillus subtilis 15A B-92 based on the 16S rRNA molecular technique. The purified pectinase from the isolate showed 99.6 U/mg specific activity and 11.6-fold purity. The molecular weight of the purified bacterial pectinase was 14.41 ± 1 kD. Optimum pectinase activity was found at pH 4.5 and 50 °C, and the enzyme was 100% stable for 3.5 h in these conditions. No enzymatic inhibition or activation effect was seen with Fe2+, Ca2+, or Mg2+. However, a slight inhibition was seen with Cu2+, Mn2+, and Zn2+. Tween 20 and 80 slightly inhibited the pectinase, whereas iodoacetic acid (IAA), ethylenediaminetetraacetate (EDTA), urea, and sodium dodecyl sulfate (SDS) showed potent inhibition. The bacterial pectinase degraded citrus pectin (100%); however, it was inactive in the presence of galactose. With citrus pectin as the substrate, the Km and Vmax were calculated as 1.72 mg/mL and 1609 U/g, respectively. The high affinity of pectinase for its substrate makes the process cost-effective when utilized in food industries. The obtained pectinase was able to clarify orange and apple juices, justifying its application in the food industry.

Tailoring the substitution pattern of Pyrrolidine-2,5-dione for discovery of new structural template for dual COX/LOX inhibition.

Dual inhibition of the enzymatic pathways of cyclooxygenases (COX-1/COX-2) and lipoxygenase (LOX) is a rational approach for developing more efficient and safe anti-inflammatory agents. Herein, dual inhibitors of COX and LOX for the management of inflammation are reported. The structural modifications of starting pyrrolidine-2,5-dione aldehyde derivatives resulted in two structurally diverse families (Family A & B). Synthesized derivatives from both Families displayed preferential COX-2 affinity in submicromolar to nanomolar ranges. Disubstitution pattern of the most active series of compounds having N-(benzyl(4-methoxyphenyl)amino moiety presents a new template that is mimic to the diaryl pattern of traditional COX-2 inhibitors. Compound 78 with IC50 value of 0.051 ± 0.001 µM emerged as the most active compound. Highly potent COX-2/5-LOX inhibitors have also demonstrated appreciable in-vivo anti-inflammatory activity through carrageenan induced paw edema test. Moreover, the involvement of histamine, bradykinin, prostaglandin, and leukotriene mediators to adjust the inflammatory response were also studied. Apart from COX inhibition, sulfonamide is considered an important template for carbonic anhydrase inhibition. Hence, we also evaluated six sulfonamide derivatives for off-target in-vitro bovine carbonic anhydrase-II inhibition. Biological results were finally rationalized by docking simulations. Typically, most active COX-2 inhibitors interact with the amino acid residues responsible for the COX-2 selectivity.

Facile one pot sonochemical synthesis of layered nanostructure of ZnS NPs/rGO nanosheets for simultaneous analysis of daclatasvir and hydroxychloroquine.

In this study, zinc sulfide nanoparticles were loaded on reduced graphene oxide (ZnS NPs/rGO) using simple sonochemical method. The nanocomposite was characterized using different morphological and electrochemical techniques such as TEM, SEM, PXRD, EDX, Raman spectroscopy, FTIR, N2-adsorption-desorption, CV, and EIS. The ZnS NPs/rGO modified glassy carbon electrode (GCE) was used to simultaneously estimate hydroxychloroquine (HCQ) and daclatasvir (DAC) in a binary mixture for the first time. The modified nanocomposite exhibited good catalytic activity towards HCQ and DAC detection. In addition, it showed higher sensitivity, good selectivity and stability; and high reproducibility towards HCQ and DAC analysis. The activity of the modified electrode was noticeably improved due to synergism between ZnS NPs and rGO. Under optimum conditions of DPV measurements, the anodic peak currents (Ipa) were obviously increased with the increase of HCQ and DAC amounts with linear ranges of 5.0-65.0 and 7.0-65.0 nM with LODs of 0.456 and 0.498 nM for HCQ and DAC, respectively. The ZnS NPs/ rGO modified GCE was used to quantify HCQ and DAC in biological fluids with recoveries of 98.7-102.7% and 96.9-104.5% and RSDs of 1.89-3.57% and 1.91-3.70%, respectively.

Cardiotonic potential of Carissa opaca Stapf ex Haines: A study on isolated rabbit heart.

Carissa opaca (C.O) is a wild shrub, belonging to the family Apocynaceae. The medicinal virtues of this plant have long been known. The present study demonstrates the effects of aqueous-methanolic extract and various fractions (n-butanolic and aqueous) of Carissa opaca on cardiovascular parameters. The perfusion pressure (PP), force of contraction (FC) and heart rate (HR) were assessed on isolated heart of rabbit using Langendroff's technique for crude extract and fractions of C.O, followed by the elucidation of the mechanism of action after estimating toxicity of the plant. Negative ionotropic and positive chronotropic effects, with an increase in PP in isolated perfused rabbit heart were observed the with plant extract and fractions. The aqueous-methanolic extract exhibited maximum response at 1mg/ml while the n-butanolic and aqueous fractions showed a maximum response at 1mg/ml and 10µg/ml respectively. Both fractions produced the same response when treated with atropine (10-5 M), however the actions of adrenaline (10-5 M) and calcium chloride (10-5 M) remained unblocked. Acute toxicity studies indicated that the plant was safe up to 2000 mg/kg and sub-chronic studies demonstrated that no significant change in haematological and biochemical parameters observed. In conclusion, this study supports the folkloric claim of C.O extract.

Ultrasensitive fluorometric determination of aluminum using the CoFe2O4 NPs/SDS/oxine system with the aid of ultrasound waves.

In this study, we present a thoughtful integration of a dispersive solid-phase sorbent and oxine for the ultrasensitive and highly selective determination of Al3+ ions. Cobalt ferrite nanoparticles (CoFe2O4 NPs) modified with oxine were employed to facilitate the pre-concentration and estimation of Al3+, forming highly fluorescent chelate. The modification process included the assistance of sodium dodecyl sulfate (SDS) and sonication. The results indicated that the fluorescence intensity of Al3+-oxine/SDS@CoFe2O4 NPs surpassed that of Al3+-oxine alone. The confirmation of the successful functionalization of CoFe2O4 NPs with oxine was established through various techniques. Under optimal conditions, the fluorescence intensity exhibited a positive correlation with increasing concentrations of Al3+ within the range of 0.029-600 ng mL-1, achieving a detection limit of 0.0087 ng mL-1 based on signal to noise ratio 3 : 1. The developed method was effectively applied to the determination of Al3+ in drinking water samples, yielding recoveries in the range of 97.19% to 103.13%, with a relative standard deviation (RSD%) not exceeding 3.78%.

Surface engineering of carbon microspheres with nanoceria wrapped on MWCNTs: a dual electrocatalyst for simultaneous monitoring of molnupiravir and paracetamol.

In the present study, nanoceria-decorated MWCNTs (CeNPs@MWCNTs) were synthesized using a simple and inexpensive process. Molnupiravir (MPV) has gained considerable attention in recent years due to the infection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Since some people infected with COVID-19 experience fever and headaches, paracetamol (PCM) has been prescribed to relieve these symptoms. Therefore, there is an urgent need to monitor and detect these drugs simultaneously in pharmaceutical and biological samples. In this regard, we developed a novel sensor based on nanoceria-loaded MWCNTs (CeNPs@MWCNTs) for simultaneous monitoring of MPV and PCM. The incorporation of CeNPs@MWCNTs electrocatalyst into a glassy carbon microsphere fluorolube oil paste electrode (GCMFE) creates more active sites, which increase the surface area, electrocatalytic ability, and electron transfer efficiency. Interestingly, CeNPs@MWCNTs modified GCMFE demonstrated excellent detection limits (6.0 nM, 8.6 nM), linear ranges (5.0-5120 nM, 8.0-4162 nM), and sensitivities (78.6, 94.3 µA µM-1 cm-2) for simultaneous detection of MPV and PCM. The developed CeNPs@MWCNTs electrocatalyst modified GCMFE exhibited good repeatability, anti-interference capability, stability, and real-time analysis with good recovery results, which clearly indicates that it can be used for real-time industrial applications.

Enhanced fluorescent detection of oxaliplatin via BSA@copper nanoclusters: a targeted approach for cancer drug monitoring.

A new fluorescence sensing approach has been proposed for the precise determination of the anti-cancer drug oxaliplatin (Oxal-Pt). This method entails synthesizing blue-emitting copper nanoclusters (CuNCs) functionalized with bovine serum albumin (BSA) as the stabilizing agent. Upon excitation at 360 nm, the resultant probe exhibits emission at 460 nm. Notably, the fluorescence response of BSA@CuNCs substantially increases upon incubation with Oxal-Pt due to multiple binding interactions between the drug and the fluorescent probe. These interactions involve hydrogen bonding, hydrophobic interaction, and the high affinity between the SH groups (cysteine residues of BSA) and platinum (in Oxal-Pt). Consequently, this interaction induces aggregation-induced emission enhancement (AIEE) of BSA@CuNCs. The probe demonstrates a broad response range from 0.08 to 140.0 µM, along with a low detection limit of 20.0 nM, determined based on a signal-to-noise ratio of 3. Furthermore, the probe effectively detects Oxal-Pt in injections, human serum, and urine samples, yielding acceptable results. This study represents a significant advancement in the development of a straightforward and efficient sensor for monitoring platinum-containing anti-cancer drugs during chemotherapy.

Enhanced fluorometric detection of histamine using red emissive amino acid-functionalized bimetallic nanoclusters.

Lysine-capped gold nanoclusters doped with silver (LYS@Ag/Au NCs) have been developed for the sensitive and selective "turn-off" fluorescence detection of histamine. This fluorescent probe demonstrates excellent stability and a high quantum yield of 9.45%. Upon addition of histamine, a positively charged biogenic amine, to the LYS@Ag/Au NCs fluorescent probe, its fluorescence emission is quenched due to electrostatic interaction, aggregation, and hydrogen bond formation. The probe exhibits good sensitivity for the determination of histamine within the range of 0.003-350 µM, with a detection limit of 0.001 µM based on a signal-to-noise ratio of 3. Furthermore, the probe has been applied to detect biogenic amines in complicated matrices, highlighting its potential for practical applications. However, interference from the analogue histidine was observed during analysis, which can be mitigated by using a Supelclean™ LC-SAX solid-phase extraction column for removal.

Dual modulation of blue-fluorescent carbon dots for simultaneous detection of topotecan and pantoprazole.

This study introduces a novel approach for the simultaneous determination of topotecan (TOP) and pantoprazole (PNT), two drugs whose interaction is critical in clinical applications. The significance of this study originates from the need to understand the pharmacokinetic changes of TOP after PNT administration, which can inform necessary dose adjustments of TOP. To achieve this, nitrogen blue emissive carbon dots (B@NCDs) were produced and employed due to their unique fluorescent properties. When TOP is added to B@NCDs, it exhibits strong native fluorescence at 545 nm without influencing the B@NCDs' fluorescence at 447 nm. Conversely, PNT causes quenching of B@NCDs fluorescence, a property that enables the distinct detection of both drugs. The B@NCDs were fully characterized using different techniques, including ultraviolet-visible spectrophotometry, fluorescence analysis, X-ray diffraction (XRD), transmission electron microscopy (TEM), and FTIR spectroscopy. The proposed method demonstrated excellent linearity, selectivity, and sensitivity, with low detection limits (LOD, S/N = 3); 0.0016 µg mL-1 for TOP and 0.36 µg mL-1 for PNT. Applied to spiked rabbit plasma samples, this method offers a new approach for evaluating the pharmacokinetic interaction between TOP and PNT. It enables the determination of all pharmacokinetic parameters of TOP before and after coadministration with PNT, providing essential insights into whether dose adjustments are necessary. This research not only contributes to the field of drug monitoring and interaction studies but also exemplifies the potential of B@NCDs in complex biological matrices, paving the way for further pharmacological and therapeutic applications.

A multi-modal approach to investigate Desmodium gangeticum's influence on stress-induced male infertility: In vivo, in vitro, and in silico assessments.

Physical and psychological stress has an inverse relation with male libido and sperm quality. The present study investigates the potential fertility-enhancing properties of Desmodium gangeticum (DG) root extracts in male Wister rats subjected to immobilization-induced stress (SIMB). DG roots were extracted using n-hexane (HEDG), chloroform (CEDG), and water (AEDG). In the pilot study, aphrodisiac protentional was investigated at two doses (125 and 250 mg kg-1) of each extract. In the main study, the HEDG and AEDG at 125 and 250 mg kg-1 were challenged for the stress by immobilization (SIMB), for 6 h daily over 28 days. Parameters assessed included aphrodisiac effects, gonadosomatic index (GSI), semen quality, sperm quantity, fructose content, serum hormonal levels, testicular oxidative stress, and testicular histopathology. Additional in silico studies, including the lipid solubility index, molecular docking, molecular dynamics, and SymMap studies were conducted for validation. HEDG demonstrated significant aphrodisiac activity, improved - GSI, sperm quality and quantity, and fructose content, serum testosterone levels, histological changes induced by SIMB in the testes. Swiss ADME studies indicated Gangetin (a pterocarpan) had a high brain permeation index (4.81), a superior docking score (-8.22), and higher glide energy (-42.60), compared with tadalafil (-7.17). The 'Lig fit Prot' plot in molecular dynamics simulations revealed a strong alignment between Gangetin and phosphodiesterase type 5 (PDE5). HEDG exerts aphrodisiac effects by increasing blood testosterone levels and affecting PDE5 activity. The protective effects on spermatozoa-related parameters and testicular histological changes are attributed to the antioxidant and anti-inflammatory properties, of pterocarpan (gangetin).

Selective detection of rutin at novel pyridinic-nitrogen-rich carbon dots derived from chicken feet biowaste: The role of bovine serum albumin during the assay.

A simple fluorescence method is described for measuring rutin dependent on the nitogen-doped carbon dots (NCDs) prepared via simple pyrolysis method from chicken feet biowaste. The as-fabricated NCDs have unique advantages including cost-effectiveness and high quantum yield (42.9 %). The as-prepared NCDs explore an optimal emission band at 430 nm following exciting NCDs at 330 nm. Addition of rutin to blue-emissive NCDs quenched their fluorescence emission by inner-filtration effect (IFE) and static quenching. Under optimized conditions, the fluorescence responses increased as the rutin amount was raised from 100 to 1000 nmol/L with 5.3 nmol/L as a detection limit (S/N = 3). The probe selectivity was improved by adding bovine serum albumin (BSA), which binds other structurally-related compounds (other flavonoids). The as-synthesized NCDs exhibited some advantages towards rutin detection such as: lower LOD value, satisfactorily reproducibility, simplicity, rapidity, selectivity, and stability. The sensing probe was efficiently utilized for determining rutin in different real samples with acceptable results. The sensor offers an efficient biowaste-based approach for the determination of (bio) molecules.

Quantitative-HPLC-DAD polyphenols analysis, anxiolytic and cognition enhancing potentials of Sorbaria tomentosa Lindl. Rehder.

ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants of the family Rosaceae have a long history of traditional uses in the management of neurological disorders. Sorbaria tomentosa Lindl. Rehder is composed of antioxidant and neuroprotective polyphenolics. AIMS OF THE STUDY: The current study was designed to explore phenolics profile via high performance liquid chromatography-photodiode array detector (HPLC-DAD) and validated the neuroprotective and anxiolytic potentials of S. tomentosa by applying in vitro and in vivo approaches. MATERIALS AND METHODS: The plant crude methanolic extract (St.Crm) and fractions were subjected to HPLC-DAD analysis for qualitative and quantitative assessment of phytochemicals. Samples were screened for in vitro free radicals scavenging assays by using 2,2-diphenylpicrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) along with acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes inhibition assays. For cognitive and anxiolytic studies, mice were subjected to open field, elevated plus maze (EPM), light-dark model, Y-maze, shallow water maze (SWM), and novel object recognition (NOR) tests. RESULTS: HPLC-DAD analysis revealed the presence of high concentrations of phenolic compounds. For instance, in St.Cr, 21 phenolics were quantified, among which apigenin-7-glucoside (291.6 mg/g), quercetin (122.1 mg/g), quercetin-3-feruloylsophoroside-7-glucoside (52.6 mg/g), quercetin-7-glucoside (51.8 mg/g), ellagic acid (42.7 mg/g), luteolin (45.0 mg/g), kaempferol (40.5 mg/g), 5-feruloylquinic acid (43.7 mg/g) were present in higher concentrations. Likewise, in ethyl acetate fraction (St.Et.Ac), 21 phenolics were identified as 3,5-di-caffeoylquinic acid (177.4 mg/g) and 5-hydroxybenzoylquinic acid (46.9 mg/g) were most abundant phytochemicals. Highly valuable phenolics were also identified in other fractions including butanol (St.Bt), chloroform (St.Chf), and n-hexane (St.Hex). The various fractions exhibited concentration dependent inhibition of free radicals in DPPH and ABTS assays. Potent AChE inhibitory potentials were revealed by the test samples with St.Chf, St.Bt and St.EtAc being the most active having an IC50 of 298.1, 580.1, and 606.47 µg mL-1, respectively. Similarly, St.Chf, St.Bt, St.EtAc and St.Cr exhibited potent BChE inhibitory activity and was observed as 59.14, 54.73, 51.35 and 49.44%, respectively. A significant improvement in the exploratory behavior was observed in open field test and stress/anxiety was relieved effectively at 50-100 mg/kg. Likewise, EPM, light-dark and NOR tests revealed an anxiolytic and memory enhancing behaviors. These effects were further corroborated from the Y-maze and SWM transgenic studies that showed considerable improvement in cognition retention. CONCLUSIONS: These findings concluded that S. tomentosa possessed potential anxiolytic and nootropic efficacies and may have therapeutic potential in neurodegenerative disorders.

Facile fabrication of boron and nitrogen co-doped carbon dots for "ON-OFF-ON" fluorescence sensing of Al3+ and F- ions in water samples.

Water contamination with harmful ions has grown to be a significant environmental issue on a global scale. Therefore, the fabrication of simple, cost-effective, and reliable sensors is essential for identifying these ions. Herein, co-doping of carbon dots with new caffeine and H3BO3-derived boron (B) and nitrogen (N) was performed (BN@CDs). The as-prepared BN@CDs probe was used for the tandem fluorescence sensing of Al3+ and F- based on "ON-OFF-ON" switches. The BN@CDs nanoswitch has a high quantum yield of 44.8% with λexc. and λem. of 360 nm and 440 nm, respectively. The probe exhibited good stability with different pH, ionic-strengths, and irradiation times. The fluorescence emission of BN@CDs was decreased as the Al3+ concentration was increased with a linear range of 0.03-90 µM and a limit of detection (S/N = 3) equal to 9.0 nM. Addition of F- restored the BN@CDs emission as F- ions form a strong and stable complex with Al3+ ions [Al(OH)3F]-. Therefore, the ratio response (F/F°) was raised by raising the F- ion concentration to the range of 0.18-80 µM with a detection limit (S/N = 3) of 50.0 nM. The BN@CDs sensor exhibits some advantages over other reported methods in terms of simplicity, high quantum yield, and low detection limit. Importantly, the sensor was successfully applied to determine Al3+ and F- in various ecological water specimens with accepted results.

Phytochemicals-based ß-amyloid cleaving enzyme-1 and MAO-B inhibitors for the treatment of Alzheimer's disease: molecular simulations-based predictions.

Alzheimer's disease (AD) is among the highly prevalent neurodegenerative disorder of the aging brain and is allied with cognitive and behavioral abnormalities. Unfortunately, there is very limited drug discovery for the effective management of AD, and the clinically approved drugs have limited efficacy. Consequently, there is an immediate demand for the development of new compounds that have the ability to act as multitarget-directed ligands (MTDLs). As major pathological targets of the disease, the current study aimed to investigate lead natural bioactive compounds including apigenin, epigallocatechin-3-gallate, berberine, curcumin, genistein, luteolin, quercetin, resveratrol for their inhibitory potentials against ß-amyloid cleaving enzyme-1 (BACE1) and monoamine oxidase-B (MAO-B) enzymes. The study compounds were docked against the target enzymes (MAO-B and BACE1) using MOE software and subsequent molecular dynamics simulations (MDS) studies. The molecular docking analysis revealed that these phytochemicals (MTDLs) showed good interactions with the target enzymes as compared to the reference inhibitors. Among these eight phytocompounds, the epigallocatechin-3-gallate compound was an active inhibitor against both drug targets, with the highest docking scores and good interactions with the active residues of the enzymes. Furthermore, the docking result of the active one inhibitor in complex with the target enzymes (epigallocatechin-3-gallate/BACE1, epigallocatechin-3-gallate/MAO-B, reference/BACE1 and reference/MAO-B) were further validated by MDS. According to the findings of our study, epigallocatechin-3-gallate has the potential to be a candidate for use in the treatment of neurological illnesses like AD. This compound has MTDL potential and may be exploited to create new compounds with disease-modifying features.Communicated by Ramaswamy H. Sarma.

Design, synthesis, antiproliferative activity, estrogen receptors binding affinity of C-3 pregnenolone-dihydropyrimidine derivatives for the treatment of breast cancer.

Breast cancer (BCa) is very common malignancy and globally, has become the second leading cause of cancer death among women. For the treatment of BCa, estrogen receptors-alpha (ERα) has proven to be a therapeutic target. In continuation of our previous reported dihydropyrimidine-based pregnenolone derivatives, we modified at C-3 hydroxyl group. Structural architecture of estrogen receptors (ER) with excellent ER binding affinity was used for modification. MTT assay was used to evaluate the synthesized steroidal analogs for their antiproliferative activities against ER-positive MCF-7, ER-negative MDA-MB-231 (ER-) breast cancer cells and non-cancerous HEK-293 cells. Structure activity relationship (SAR) studies revealed that diethanolamine containing pregnenolone derivatives showed significant cytotoxicity against ER + MCF-7 and also showed good binding affinity with ERα and are relatively safe against HEK-293 cell model. Docking studies demonstrated that high binding affinity of diethanolamine analogs is due to their binding interaction with key amino acid residues present in the binding site of Erα.

Cephalosporin as Potent Urease and Tyrosinase Inhibitor: Exploration through Enzyme Inhibition, Kinetic Mechanism, and Molecular Docking Studies.

In present study, eleven cephalosporin drugs were selected to explore their new medically important enzyme targets with inherited safety advantage. To this end, selected drugs with active ingredient, cefpodoxime proxetil, ceftazidime, cefepime, ceftriaxone sodium, cefaclor, cefotaxime sodium, cefixime trihydrate, cephalexin, cefadroxil, cephradine, and cefuroxime, were evaluated and found to have significant activity against urease (IC50 = 0.06 ± 0.004 to 0.37 ± 0.046 mM) and tyrosinase (IC50 = 0.01 ± 0.0005 to 0.12 ± 0.017 mM) enzymes. Urease activity was lower than standard thiourea; however, tyrosinase activity of all drugs outperforms (ranging 6 to 18 times) the positive control: hydroquinone (IC50 = 0.18 ± 0.02 mM). Moreover, the kinetic analysis of the most active drugs, ceftriaxone sodium and cefotaxime sodium, revealed that they bind irreversibly with both the enzymes; however, their mode of action was competitive for urease and mixed-type, preferentially competitive for tyrosinase enzyme. Like in vitro activity, ceftriaxone sodium and cefotaxime sodium docking analysis showed their considerable binding affinity and significant interactions with both urease and tyrosinase enzymes sufficient for downstream signaling responsible for observed enzyme inhibition in vitro, purposing them as potent candidates to control enzyme-rooted obstructions in future.

Antioxidant Molecules Isolated from Edible Prostrate Knotweed: Rational Derivatization to Produce More Potent Molecules.

Prostrate knotweed also called Polygonum aviculare is an important edible plant. The polygonum is majorly known for the phenolics and antioxidants. The antioxidants combat the excessive free radicals within the body. The excessive free radicals are implicated in various other diseases like diabetes, Alzheimer's, and inflammation. This study was aimed at exploring the antioxidant bioactives and their derivatizations to produce new molecules with advanced pharmacological features. We have isolated six compounds (1-6) from Polygonum aviculare. Furthermore, rational-based chemical derivatives for compound 5 have been formed for the management of diabetes, Alzheimer's, and inflammation. In preliminary antioxidant studies, all the isolated compounds (1-6) showed potential results against DPPH and ABTS free radicals. Based on the IC50 and chemical nature of the compounds, compound 5 was subjected to derivatization. Keeping the phenolic part of compound 5 unaffected, hydroxy succinimide (5A) and thiazolidinedione (5B) were synthesized. The compound 5A was found to be a potent inhibitor of AChE, BChE, COX-1, COX-2, 5-LOX, and DPPH giving IC50 values of 10.60, 15.10, 13.91, 1.08, 0.71, and 1.05 µM, respectively. The COX-2 selectivity of compound 5A was found at 12.9. The compound 5B was found to be a potent multitarget antidiabetic agent giving IC50 values of 15.34, 21.83, 53.28, and 1.94 µM against α-glucosidase, α-amylase, protein tyrosine phosphatase 1B, and DPPH. Docking studies were performed to manipulate the binding interactions. The docking pose of all the tested compounds was found to have increased binding affinity against all tested targets that supported the in vitro results. Our results showed that Polygonum aviculare is a rich source of antioxidant compounds. The two new derivatives have enhanced pharmacological features to treat diabetes, inflammation, and Alzheimer's disease.

Phytochemistry, anti-diabetic and antioxidant potentials of Allium consanguineum Kunth.

AIM: The study was planned to investigate the phytochemicals, antidiabetic and antioxidant studies of A. consanguineum. METHODS: The preliminary studies were performed on crude extract and different solvent fractions. Based on the potency, the chloroform fraction was semi-purified to phyto-fractions CHF-1 - 5. Furthermore, CHF-3 was subjected to isolation of pure compounds using column chromatography. The α-glucosidase, α-amylase and antioxidant assays (DPPH, ABTS, H2O2) were performed on all samples. The in-vivo experiments on compounds 1 and 2 were also performed using oral glucose tolerance test. Docking studies were performed on α-glucosidase and α-amylase targets. RESULTS: Among all fractions, the chloroform fraction exhibited excellent activities profile giving IC50 values of 824, 55, 117, 58 and 85 µg/ml against α-glucosidase, α-amylase, DPPH, ABTS and H2O2 targets respectively. Among the five semi-purified chloroform phyto-fractions (CHF-1-5), CHF-3 was the leading fraction in activities giving IC50 values of 85.54, 61.19 and 26.58 µg/ml against α-glucosidase, α-amylase and DPPH respectively. Based on the overall potency and physical amount of CHF-3, it was subjected to purification to get compounds 1 and 2. The two compounds were also found potent in in-vitro activities. The observed IC50 values for compound 1 were 7.93, 28.01 and 6.19 µg/ml against α-glucosidase, α-amylase and DPPH respectively. Similarly, the compound 2 exhibited IC50 of 14.63, 24.82 and 7.654 µg/ml against α-glucosidase, α-amylase and DPPH respectively. Compounds 1 and 2 were potent in decreasing the blood glucose levels in experimental animals. Compounds 1 and 2 also showed interactions with the respective enzymes with molecular docking. CONCLUSIONS: We can conclude that A. Consanguineum is a rich source of natural antidiabetic agents. Bioguided isolation of compound 1 and 2 showed potential inhibitions in all tested in-vitro antidiabetic targets. Further, both the compounds were also able to decrease the blood glucose levels in experimental animals.