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Zingiber officinale var. rubrum is known as ‘Halia bara’ in the Southeast Asia region. Many herbal products containing Halia bara are in the market are being used for either cosmetic purposes or well-being. The present study aims to develop a simple, high-performance liquid chromatography (HPLC) method using a diode array detector for the quantification of predominant gingerols (4-, 6-, 8-, and 10-) and shogaols (6-, 8-, and 10-) in supercritical carbon dioxide extract of Halia bara. The optimum conditions for elution of seven compounds were: column, ODS Genesis; column temperature, 25 C; elution, gradient elution consisting of acetonitrile and aqueous formic acid; detection wavelength, 282 nm; flow rate, 1 mL/min; injection volume, 20 µL; and run-time, 38 min. The optimized HPLC method was validated for linear range, accuracy, precision (repeatability and reproducibility), sensibility (limit of detection and quantification) and recovery. All the validation parameters were within the permissible limits stipulated by the International Council of Harmonization guidelines. In Halia bara supercritical fluid-carbon dioxide extract, the amounts of bioactive constituents are in the decreasing order of 10-gingerol, 6-gingerol, 6-shogaol, 8- gingerol, 8-shogaol, 10-shogaol and 4-gingerol.

This is the first study investigating the nuclear factor (erythroid-derived 2)-like 2 (NRF2) activity of compounds containing a new scaffold, tetrahydrobenzo[b]thiophene. Eighteen compounds were synthesised and confirmed their NRF2 activation through NQO1 enzymatic activity and mRNA expression of NQO1 and HO-1 in Hepa-1c1c7 cells. The compounds disrupted the interaction between Kelch-like ECH-associated protein 1 (KEAP1) and NRF2 via interfering with the KEAP1's Kelch domain. The compounds exhibited anti-inflammatory activity in Escherichia coli Lipopolysaccharide (LPS

A novel series of amide functionalized imidazo[1,2-a]pyridine (14a–14j) derivatives were synthesized and screened for their anticancer activities against breast (MCF-7 and MDA-MB-231), lung (A549), and prostate (DU-145) cancer cell lines using MTT assay with etoposide as the standard reference drug. Among them, compound 14j showed highest potency in anticancer activities against MCF-7, MDA-MB-231, A549, and DU-145 cell lines with IC50 values of 0.021 ± 0.0012 µM, 0.95 ± 0.039 µM, 0.091 ± 0.0053 µM, and 0.24 ± 0.032 µM, respectively.

Molecules possessing harmine moiety are reported to exhibit marked fungicidal and bactericidal activities. In this study, various quinozilinium tetrafluoroborate salts were synthesized using acylic and cyclic oxoketene dithioacetals followed by cycloaromatization from Harmine. All of these synthesized compounds were characterized by 1H NMR, 13C NMR, Mass and CHN analysis. This methodology would find wide usage in the preparation of indolo quinozilinium -based library of small molecules useful for medicinal chemistry and in drug discovery.

This study’s objective was to examine L-arginine (L-arg) supplementation’s effect on mono-species biofilm (Streptococcus mutans/Streptococcus sanguinis) growth and underlying enamel substrates. The experimental groups were 1%, 2%, and 4% arg, and 0.9% NaCl was used as the vehicle control. Sterilised enamel blocks were subjected to 7-day treatment with test solutions and S. mutans/S. sanguinis inoculum in BHI. Post-treatment, the treated biofilms stained for live/dead bacterial cells were analysed using confocal microscopy. The enamel specimens were analysed using X-ray diffraction crystallography (XRD), Raman spectroscopy (RS), and transmission electron microscopy (TEM). The molecular interactions between arg and MMP-2/MMP-9 were determined by computational molecular docking and MMP assays. With increasing arg concentrations, bacterial survival significantly decreased (p &lt, 0.05). The XRD peak intensity with 1%/2% arg was significantly higher than with 4% arg and the control (p &lt, 0.05). The bands associated with the mineral phase by RS were significantly accentuated in the 1%/2% arg specimens compared to in other groups (p &lt, 0.05). The TEM analysis revealed that 4% arg exhibited an ill-defined shape of enamel crystals. Docking of arg molecules to MMPs appears feasible, with arg inhibiting MMP-2/MMP-9 (p &lt, 0.05). L-arginine supplementation has an antimicrobial effect on mono-species biofilm. L-arginine treatment at lower (1%/2%) concentrations exhibits enamel hydroxyapatite stability, while the molecule has the potential to inhibit MMP-2/MMP-9.

Artificial intelligence (AI) in drug discovery and development (DDD) has gained more traction in the past few years. Many scientific reviews have already been made available in this area. Thus, in this review, the authors have focused on the success stories of AI-driven drug candidates and the scientometric analysis of the literature in this field.The authors explore the literature to compile the success stories of AI-driven drug candidates that are currently being assessed in clinical trials or have investigational new drug (IND) status. The authors also provide the reader with their expert perspectives for future developments and their opinions on the field.Partnerships between AI companies and the pharma industry are booming. The early signs of the impact of AI on DDD are encouraging, and the pharma industry is hoping for breakthroughs. AI can be a promising technology to unveil the greatest successes, but it has yet to be proven as AI is still at the embryonic stage.

The successful regulatory authority approval rate of drug candidates in the drug development pipeline is crucial for determining pharmaceutical research and development (R&D) efficiency. Regulatory authorities include the US Food and Drug Administration (FDA), European Medicines Agency (EMA), and Pharmaceutical and Food Safety Bureau Japan (PFSB), among others. Optimal drug metabolism and pharmacokinetics (DMPK) properties influence the progression of a drug candidate from the preclinical to the clinical phase. In this review, we provide a comprehensive assessment of essential concepts, methods, improvements, and challenges in DMPK science and its significance in drug development. This information provides insights into the association of DMPK science with pharmaceutical R&D efficiency.

Two new alkyl (E)-5-(methylsulfinyl) pent-4-enoates were isolated from the seeds of Raphanus sativus L., Brassicaceae. The compounds were identified as methyl-(E)-5-(methylsulfinyl) pent-4-enoate and ethyl-(E)-5-(methylsulfinyl) pent-4-enoate using 1D and 2D NMR and HR-EI-MS.

Objectives: The aim of the current project was to study the antimicrobial efficacy of a newly developed irrigant, k21/E against E. faecalis biofilm. Methods: Root canals were instrumented and randomly divided into the following groups: irrigation with saline, 6% NaOCl (sodium hypochlorite), 6% NaOCl + 2% CHX (Chlorhexidine), 2% CHX, 0.5% k21/E (k21 - quaternary ammonium silane) and 1% k21/E. E. faecalis were grown (3-days) (1 × 10 CFU mL), treated, and further cultured for 11-days. Specimens were subjected to SEM, confocal and Raman analysis and macrophage vesicles characterized along with effect of lipopolysaccharide treatment. 3T3 mouse-fibroblasts were cultured for alizarin-red with Sortase-A active sites and Schrodinger docking was performed. TEM analysis of root dentin substrate with matrix metalloproteinases profilometry was also included. A cytotoxic test analysis for cell viability was measured by absorbance of human dental pulp cells after exposure to different irrigant solutions for 24 h. The test percentages have been highlighted in Table 1. Results: Among experimental groups, irrigation with 0.5% k21/E showed phase separation revealing significant bacterial reduction and lower phenylalanine 1003 cm and Amide III 1245 cm intensities. Damage was observed on bacterial cell membrane after use of k21/E. No difference in exosomes distribution between control and 0.5%k21/E was observed with less TNFα (*p < 0.05) and preferential binding of SrtA. TEM images demonstrated integrated collagen fibers in control and 0.5%k21/E specimens and inner bacterial membrane damage after k21/E treatment. The k21 groups appeared to be biocompatible to the dental pulpal cells grown for 24 h. Significance: Current investigations highlight potential advantages of 0.5% k21/E as irrigation solution for root canal disinfection.

To determine whether quaternary ammonium (k21) binds to Severe Acute Respiratory Syndrome–Coronavirus 2 (SARS-CoV-2) spike protein via computational molecular docking simulations, the crystal structure of the SARS-CoV-2 spike receptor-binding domain complexed with ACE-2 (PDB ID: 6LZG) was downloaded from RCSB PD and prepared using Schrodinger 2019-4. The entry of SARS-CoV-2 inside humans is through lung tissues with a pH of 7.38–7.42. A two-dimensional structure of k-21 was drawn using the 2D-sketcher of Maestro 12.2 and trimmed of C18 alkyl chains from all four arms with the assumption that the core moiety k-21 was without C18. The immunogenic potential of k21/QA was conducted using the C-ImmSim server for a position-specific scoring matrix analyzing the human host immune system response. Therapeutic probability was shown using prediction models with negative and positive control drugs. Negative scores show that the binding of a quaternary ammonium compound with the spike protein’s binding site is favorable. The drug molecule has a large Root Mean Square Deviation fluctuation due to the less complex geometry of the drug molecule, which is suggestive of a profound impact on the regular geometry of a viral protein. There is high concentration of Immunoglobulin M/Immunoglobulin G, which is concomitant of virus reduction. The proposed drug formulation based on quaternary ammonium to characterize affinity to the SARS-CoV-2 spike protein using simulation and computational immunological methods has shown promising findings.

Background Swietenia macrophylla seeds possess diverse biological activities in which inflammation is the primary cause, and swietenine is the main tetranortriterpenoid present. Purpose The purpose of the study is to investigate the molecular mechanisms involved in the anti-inflammatory activity of swietenine and its cytoprotective effect. Methods The anti-inflammatory activity of swietenine and its molecular mechanisms were evaluated using LPSEc- stimulated RAW 264.7 cells. The cytoprotective effect of swietenine was evaluated via determining NRF2 inducing activity in Hepa-1c1c7 cells. The in vitro metabolic stability of swietenine was assessed using mouse, rat and human liver microsomes. Results Swietenine showed dose-dependent effect in inhibiting NO production, downregulating pro-inflammatory cytokines (IL-1β, IFN-γ, TNF-α, and IL-6) and mediators (NF-κB and COX-2); and increasing the levels of NRF2, and HO-1 in LPSEc-stimulated RAW264.7 cells. Swietenine also induced NQO1 activity, a classical marker of NRF2 activation, in Hepa-1c1c7 cells. In addition, swietenine was metabolically stable in mouse, rat, and human liver microsomes. Conclusion The results suggest that the anti-inflammatory effect of swietenine is mediated by the down-regulation of pro-inflammatory cytokines and mediators and the activation of cytoprotective NRF2/HO-1 pathway.

Novel 3D-biomaterial scaffold is constructed having a combination of a new quaternary ammonium silane (k21) antimicrobial impregnated in 3D collagen printed scaffolds cross linked with Riboflavin in presence of d-alpha-tocopheryl poly(ethyleneglycol)-1000-succinate. Groups of "0.1% and 0.2% k21", and "0.1% and 0.2% Chlorhexidine (CHX)" are prepared. k21/CHX with neutralized collagen is printed with BioX. Riboflavin is photo-activated and examined using epifluorescence for Aggregatibacter actinomycetemcomitans (7-days). Collagen is examined using TEM and measured for porosity, and shape-fitting. Raman and tandem mass/solid-state are performed with molecular-docking and circular-dichroism. X-ray diffractions, rheological tests, contact angle, and ninhydrin assay are conducted. k21 samples demonstrated collagen aggregates while 0.1% CHX and 0.2% CHX showed irregularities. Porosity of control and "0.1% and 0.2% k21" scaffolds show no differences. Low contact angle, improved elastic-modulus, rigidity, and smaller strain in k21 groups are seen. Bacteria are reduced and strong organic intensities are seen in k21 scaffolds. Simulation shows hydrophobicity/electrostatic interaction. Crosslinking is observed in 0.2% CHX/79% and 0.2% k21/80%. Circular dichroism for k21 are suggestive of triple helix. XRD patterns appear at d = 5.97, 3.03, 2.78, 2.1, and 2.90 A°. 3D-printing of collagen impregnated with quaternary ammonium silane produces a promising scaffold with antimicrobial potency and structural stability.

Objective Here we describe a novel formulation, based on quaternary ammonium (QA) and riboflavin (RF), which combines antimicrobial activities and protease inhibitory properties with collagen crosslinking without interference to bonding capabilities, was investigated. Methods Experimental adhesives modified with different fractions of dioctadecyldimethyl ammonium bromide quaternary ammonium and riboflavin (QARF) were formulated. Dentine specimens were bonded to resincomposites with control or the experimental adhesives to be evaluated for bond strength, interfacial morphology, micro-Raman analysis, nano-CT and nano-leakage expression. In addition, the antibacterial and biocompatibilities of the experimental adhesives were investigated. The endogenous proteases activities and their molecular binding-sites were studied. Results Modifying the experimental adhesives with QARF did not adversely affect micro-tensile bond strength or the degree of conversion along with the demonstration of anti-proteases and antibacterial abilities with acceptable biocompatibilities. In general, all experimental adhesives demonstrated favourable bond strength with increased and improved values in 1% QARF adhesive at 24 h (39.2 ± 3.0 MPa) and following thermocycling (34.8 ± 4.3 MPa). Significance It is possible to conclude that the use of QARF with defined concentration can maintain bond strength values when an appropriate protocol is used and have contributed in ensuring a significant decrease in microbial growth of biofilms. Incorporation of 1% QARF in the experimental adhesive lead to simultaneous antimicrobial and anti-proteolytic effects with low cytotoxic effects, acceptable bond strength and interfacial morphology.

To study the antimicrobial effects of quaternary ammonium silane (QAS) exposure on Streptococcus mutans and Lactobacillus acidophilus bacterial biofilms at different concentrations. Streptococcus mutans and Lactobacillus acidophilus biofilms were cultured on dentine disks, and incubated for bacterial adhesion for 3-days. Disks were treated with disinfectant (experimental QAS or control) and returned to culture for four days. Small-molecule drug discovery-suite was used to analyze QAS/Sortase-A active site. Cleavage of a synthetic fluorescent peptide substrate, was used to analyze inhibition of Sortase-A. Raman spectroscopy was performed and biofilms stained for confocal laser scanning microscopy (CLSM). Dentine disks that contained treated dual-species biofilms were examined using scanning electron microscopy (SEM). Analysis of DAPI within biofilms was performed using CLSM. Fatty acids in bacterial membranes were assessed with succinic-dehydrogenase assay along with time-kill assay. Sortase-A protein underwent conformational change due to QAS molecule during simulation, showing fluctuating alpha and beta strands. Spectroscopy revealed low carbohydrate intensities in 1% and 2% QAS. SEM images demonstrated absence of bacterial colonies after treatment. DAPI staining decreased with 1% QAS (p p

Summary Blueberries, a functional food, are rich in bioactive polyphenols and anthocyanins. However, the shelf life is short and requires cold storage. This study provides evidence that edible foxtail millet flour (FMF) efficiently sorbs only blueberry bioactive components (polyphenols and anthocyanins) but not sugars, improves their stability and retains the activity. The concentration of blueberry polyphenols and anthocyanins sorbed to FMF ranged from 6 to 113 and 4 to 41 mg g−1, respectively. The concentration of bioactive components in one serving of blueberries (73 g) is equivalent to those present in 1.2 g of blueberry-enriched foxtail millet flour (BFMF). The blueberry bioactive sorbed onto FMF remained stable for at least 16 weeks at 40 °C. BFMF eluates inhibited α-glucosidase enzyme activity and scavenged the free radicals conferring that blueberry bioactive components in BFMF retained the activity. The sorption process described here provides a practical way of creating low glycemic protein-rich edible flour enriched with plant bioactive compounds without sugars.

The search for effective and non-invasive delivery modules to transport therapeutic molecules across skin has led to the discovery of a number of nanocarriers (viz.: liposomes, ethosomes, dendrimers, etc.) in the last few decades. However, available literature suggests that these delivery modules face several issues including poor stability, low encapsulation efficiency, and scale-up hurdles. Recently, carbon nanotubes (CNTs) emerged as a versatile tool to deliver therapeutics across skin. Superior stability, high loading capacity, well-developed synthesis protocol as well as ease of scale-up are some of the reason for growing interest in CNTs. CNTs have a unique physical architecture and a large surface area with unique surface chemistry that can be tailored for vivid biomedical applications. CNTs have been thus largely engaged in the development of transdermal systems such as tuneable hydrogels, programmable nonporous membranes, electroresponsive skin modalities, protein channel mimetic platforms, reverse iontophoresis, microneedles, and dermal buckypapers. In addition, CNTs were also employed in the development of RNA interference (RNAi) based therapeutics for correcting defective dermal genes. This review expounds the state-of-art synthesis methodologies, skin penetration mechanism, drug liberation profile, loading potential, characterization techniques, and transdermal applications along with a summary on patent/regulatory status and future scope of CNT based skin therapeutics.

Wounds still pose a huge burden on human health and healthcare systems in many parts of the world. Phytomedicines are being used to heal the wounds since ancient times. Now-a-days also many researchers are exploring the wound healing activity of phytomedicines. Wound healing is a complex process thus, it is always a question mark regarding the best test model (in vivo, ex vivo and in vitro) model to assess the wound healing activity of phytomedicines. In general, the researchers would opt for in vivo model - probably because of closer physiological relevance to human wounds. However, in vivo experimental models are not suitable for high throughput screening and not ethical in terms of initial screening of the phytomedicines. The in vivo models are associated with difficulties in obtaining the ethical approvals, requires huge budget, and resources. We argue that judicious selection of cell types would serve the purpose of developing a physiologically relevant in vitro experimental model. A lot of progress has been made in molecular biology techniques to bridge the gap between in vitro models and their physiological relevance. The in vitro models are the best suited for high throughput screening and to elucidate the molecular mechanisms. The main aim of this review is to provide insights on selection of the cell types for developing physiologically relevant in vitro wound healing assays, which can be used to improve the value of phytomedicines further.

Diabetes mellitus or type-2 diabetes, commonly referred as diabetes, is a metabolic disorder that results in high blood sugar level. Despite the availability of several antidiabetic drugs in the market, they still do not adequately regulate blood sugar levels. Thus, in general people prefer to use herbal supplements/medicines along with antidiabetic drugs to control blood sugar levels. One of such herbal medicine is Swietenia macrophylla seeds. It is widely used in Asia for controlling blood sugar levels. One of the major bioactive compounds, Swietenine, is reported to be responsible for controlling blood glucose levels. However, there were no studies on its efficacy in controlling the blood glucose in diabetic rats. In this study, we evaluated the antihyperglycemic activity of Swietenine and its pharmacodynamic interaction with Metformin in Streptozotocin induced diabetes in rats. The activity of Swietenine was investigated at three different doses: 10, 20 and 40 mg/kg body weight (bw). Metformin (50 mg/kg bw) was used as a standard drug. Swietenine (20 and 40 mg/kg bw) and Metformin (50 mg/kg bw) showed significant effect in reducing the glucose, cholesterol, triglycerides, low-density lipoprotein, urea, creatinine, alanine transaminase, alkaline phosphatase, aspartate transaminase, alanine transaminase, and malondialdehyde level in serum while it had increased the high-density lipoprotein, glutathione, and total antioxidant capacity level. In addition, Swietenine (20 and 40 mg/kg) had shown significant synergistic effect with Metformin. Administration of Swietenine at 10 mg/kg bw neither showed activity nor influenced Metformin’s activity. The results from this study confirmed the beneficial effects of Swietenine and its synergistic action with Metformin in controlling the dysregulated serum parameters in Streptozotocin induced diabetes in rats.

Background The transcription factor Nuclear factor erythroid-2-related factor 2 (NRF2) and its principal repressive regulator, Kelch-like ECH-associated protein 1 (KEAP1), are perilous in the regulation of inflammation, as well as maintenance of homeostasis. Thus, NRF2 activation is involved in cytoprotection against many inflammatory disorders. N′-Nicotinoylquinoxaline-2-carbohdyrazide (NQC) was structurally designed by the combination of important pharmacophoric features of bioactive compounds reported in the literature. Methods NQC was synthesised and characterised using spectroscopic techniques. The compound was tested for its anti-inflammatory effect using Lipopolysaccharide from Escherichia coli (LPSEc) induced inflammation in mouse macrophages (RAW 264.7 cells). The effect of NQC on inflammatory cytokines was measured using enzyme-linked immune sorbent assay (ELISA). The Nrf2 activity of the compound NQC was determined using ‘Keap1:Nrf2 Inhibitor Screening Assay Kit’. To obtain the insights on NQC’s activity on Nrf2, molecular docking studies were performed using Schrödinger suite. The metabolic stability of NQC was determined using mouse, rat and human microsomes. Results NQC was found to be non-toxic at the dose of 50 µM on RAW 264.7 cells. NQC showed potent anti-inflammatory effect in an in vitro model of LPSEc stimulated murine macrophages (RAW 264.7 cells) with an IC50 value 26.13 ± 1.17 µM. NQC dose-dependently down-regulated the pro-inflammatory cytokines [interleukin (IL)-1β (13.27 ± 2.37 μM), IL-6 (10.13 ± 0.58 μM) and tumor necrosis factor (TNF)-α] (14.41 ± 1.83 μM); and inflammatory mediator, prostaglandin E2 (PGE2) with IC50 values, 15.23 ± 0.91 µM. Molecular docking studies confirmed the favourable binding of NQC at Kelch domain of Keap-1. It disrupts the Nrf2 interaction with kelch domain of keap 1 and its IC50 value was 4.21 ± 0.89 µM. The metabolic stability studies of NQC in human, rat and mouse liver microsomes revealed that it is quite stable with half-life values; 63.30 ± 1.73, 52.23 ± 0.81, 24.55 ± 1.13 min; microsomal intrinsic clearance values; 1.14 ± 0.31, 1.39 ± 0.87 and 2.96 ± 0.34 µL/min/g liver; respectively. It is observed that rat has comparable metabolic profile with human, thus, rat could be used as an in vivo model for prediction of pharmacokinetics and metabolism profiles of NQC in human. Conclusion NQC is a new class of NRF2 activator with potent in vitro anti-inflammatory activity and good metabolic stability.

A series of novel chalcone derivatives pyrido[4,3-b]pyrazin-5(6H)-one (10a-j) were designed, synthesized and their structures were confirmed by 1H NMR, 13C NMR and mass spectral data. Further, all derivatives were tested for their anticancer activities against five human cancer cell lines such as MCF-7 (breast cancer), A-549 (lung cancer), Colo-205 (colon cancer), A2780 (ovarian cancer) and DU-145 (prostate cancer) by employing MTT assay. The clinically used drug etoposide was used as standard reference and the anticancer activity was expressed as the IC50 in µM. Among the ten compounds examined compounds, 10b, 10c, 10d, 10h, and 10i possessed more promising anticancer activity. A molecular docking study implying ATR kinase was carried out to observe the binding mode of chalcone derivatives pyrido[4,3-b]pyrazin-5(6H)-one (10a-j) on the active site of ATR kinase. The most promising compound, 10h showed π − π stacking interaction of trimethoxy phenyl and pyridone moiety with the residue Trp850, while the carbonyl (α,β-unsaturated carbonyl) and methoxy functions showed H-bond interaction with the residue Ser773 and Thr856 respectively.

Aim Novel k21 PLGA nanoparticles (nano-PLGA-RF/VE-TPGS0.50⁞k21) with synergistic effect of VE-TPGS with riboflavin-5-phospshate solution were used to analyze structural integrity, chemical interactions, antimicrobial resistance, mechanical properties as a delivery tool to acid-demineralized dentine-substrates. Materials and methods Synthesized spherical nano-PLGA ⋮ RF/VE-TPGS0.50⁞k21 were assessed for drug-encapsulation and release, antibacterial-profile, MTT, molecular simulation for MMP-2 and MMP-9 and Raman spectroscopy. Results k21 favoured increase in colloidal-size with positive zeta potential. Bands indicated k21 entrapment as nanoparticles were confined inside tubules with no effect on μTBS. XP-GScores were −2.383 and −4.383 for MMP-2 and -9. HYP liberation recorded with collagenase degradation resistance in nano-PLGA ⋮ RF/VE-TPGS0.50⁞k21 specimens. Conclusion Nano-PLGA ⋮ RF/VE-TPGS0.50⁞k21 specimens exhibited superior antibacterial/antibiofilm effects against cariogenic biofilms after bonding-resins infiltration without adversely affecting bond strength.

An efficient and convenient approach for the microwave-assisted synthesis of dimers of 1,2,3-triazole-benzofuran bearing alkyl spacer derivatives 7a-j through intermediate, bis-1,2,3-triazoles carrying alkyl spacer compounds 5a-e has been developed in excellent yields. Antimicrobial and antioxidant activities were tested for all the synthesized compounds. Among them, compoubd 7b showed potent antibacterial activity against gram positive bacteria, Where as another compound 7j exhibited potent antioxidant activity through DPPH method.

To determine the antibacterial effect of propolis nanoparticles (PNs) as an endodontic irrigant against Enterococcus faecalis biofilm inside the endodontic root canal system. Two-hundred-ten extracted human teeth were sectioned to obtain 6 mm of the middle third of the root. The root canal was enlarged to an internal diameter of 0.9 mm. The specimens were inoculated with E. faecalis for 21 days. Following this, specimens were randomly divided into seven groups, with 30 dentinal blocks in each group including: group I—saline, group II—propolis 100 µg/mL, group III—propolis 300 µg/mL, group IV—propolis nanoparticle 100 µg/mL, group V—propolis nanoparticle 300µg/mL, group VI—6% sodium hypochlorite, group VII—2% chlorhexidine. Dentin shavings were collected at 200 and 400 μm depths, and total numbers of CFUs were determined at the end of one, five, and ten minutes. The non-parametric Kruskal–Wallis and Mann–Whitney tests were used to compare the differences in reduction in CFUs between all groups, and probability values of p &lt, 0.05 were set as the reference for statistically significant results. The antibacterial effect of PNs as an endodontic irrigant was also assessed against E. faecalis isolates from patients with failed root canal treatment. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were also performed after exposure to PNs. A Raman spectroscope, equipped with a Leica microscope and lenses with curve-fitting Raman software, was used for analysis. The molecular interactions between bioactive compounds of propolis (Pinocembrin, Kaempferol, and Quercetin) and the proteins Sortase A and β-galactosidase were also understood by computational molecular docking studies. PN300 was significantly more effective in reducing CFUs compared to all other groups (p &lt, 0.05) except 6% NaOCl and 2% CHX (p &gt, 0.05) at all time intervals and both depths. At five minutes, 6% NaOCl and 2% CHX were the most effective in reducing CFUs (p &lt, 0.05). However, no significant difference was found between PN300, 6% NaOCl, and 2% CHX at 10 min (p &gt, 0.05). SEM images also showed the maximum reduction in E. faecalis with PN300, 6% NaOCl, and 2% CHX at five and ten minutes. CLSM images showed the number of dead cells in dentin were highest with PN300 compared to PN100 and saline. There was a reduction in the 484 cm−1 band and an increase in the 870 cm−1 band in the PN300 group. The detailed observations of the docking poses of bioactive compounds and their interactions with key residues of the binding site in all the three docking protocols revealed that the interactions were consistent with reasonable docking and IFD docking scores. PN300 was equally as effective as 6% NaOCl and 2% CHX in reducing the E. faecalis biofilms.

In a search for potent antileishmanial drug candidates, eighteen rhodacyanine analogues bearing fluorine or perfluoroalkyl substituents at various positions were synthesized. These compounds were tested for their inhibitory activities against Leishmania martiniquensis and L. orientalis. This ‘fluorine-walk’ analysis revealed that the introduction of fluorine atom at C-5, 6, 5′, or 6′ on the benzothiazole units led to significant enhancement of the activity, correlating with the less negative reduction potentials of the fluorinated analogues confirmed by the electrochemical study. On the other hand, CF3 and OCF3 groups were found to have detrimental effects, which agreed with the poor aqueous solubility predicted by the in silico ADMET analysis. In addition, some of the analogues including the difluorinated species showed exceptional potency against the promastigote and axenic amastigote stages (IC50 = 40–85 nM), with the activities surpassing both amphotericin B and miltefosine.

Artificial intelligence (AI) uses personified knowledge and learns from the solutions it produces to address not only specific but also complex problems. Remarkable improvements in computational power coupled with advancements in AI technology could be utilised to revolutionise the drug development process. At present, the pharmaceutical industry is facing challenges in sustaining their drug development programmes because of increased R&D costs and reduced efficiency. In this review, we discuss the major causes of attrition rates in new drug approvals, the possible ways that AI can improve the efficiency of the drug development process and collaboration of pharmaceutical industry giants with AI-powered drug discovery firms.

Treatment of glioblastoma multiforme (GBM) is a predominant challenge in chemotherapy due to the existence of blood-brain barrier (BBB) which restricts delivery of chemotherapeutic agents to the brain together with the problem of drug penetration through hard parenchyma of the GBM. With the structural and mechanistic elucidation of the BBB under both physiological and pathological conditions, it is now viable to target central nervous system (CNS) disorders utilizing the presence of transferrin (Tf) receptors (TfRs). However, overexpression of these TfRs on the GBM cell surface can also help to avoid restrictions of GBM cells to deliver chemotherapeutic agents within the tumor. Therefore, targeting of TfR-mediated delivery could counteract drug delivery issues in GBM and create a delivery system that could cross the BBB effectively to utilize ligand-conjugated drug complexes through receptor-mediated transcytosis. Hence, approach towards successful delivery of antitumor agents to the gliomas has been making possible through targeting these overexpressed TfRs within the CNS and glioma cells. This review article presents a thorough analysis of current understanding on Tf-conjugated nanocarriers as efficient drug delivery system.

Cancer is estimated to be a significant health problem of the 21st century. The situation gets even tougher when it comes to its treatment using chemotherapy employing synthetic anticancer molecules with numerous side effects. Recently, there has been a paradigm shift toward the adoption of herbal drugs for the treatment of cancer. In this context, a suitable delivery system is principally warranted to deliver these herbal biomolecules specifically at the tumorous site. To achieve this goal, carbon nanotubes (CNTs) have been widely explored to deliver anticancer herbal molecules with improved therapeutic efficacy and safety. This review uniquely expounds the biopharmaceutical, clinical and safety aspects of different anticancer herbal drugs delivered through CNTs with a cross-talk on their outcomes. This review will serve as a one-stop-shop for the readers on various anticancer herbal drugs delivered through CNTs as a futuristic delivery device.

Eugenol and eugenol-containing plants are used in ethno and modern medicine for various biological activities including antimicrobial activity. This review article provides an insightful transformation of eugenol from being an ethnomedicine to being a food protectant in the food industry. Scientific publications on the antimicrobial activity of eugenol and its respective advancements were collected from scientific databases such as Scopus, PubMed, and Google Scholar published between 1995 and June 2018. The eugenol has shown significant broad-spectrum antimicrobial activities against Gram-positive, Gram-negative, fungi, and virus. The eugenol has also shown synergistic effects with conventional antimicrobials. Formulations, such as micro- and nanoemulsions, nanocapsules, and nanoparticles, are prepared to improve the aqueous solubility and efficacy of eugenol. Eugenol is used as a food protectant in storing plants, grains, fruits, and livestock. This review covers eugenol's antimicrobial activities, formulations to improve aqueous solubility, and applications in the food industry. Extensive scientific investigations validated the ethnomedicinal uses of eugenol as an antimicrobial agent. Its activity on multidrug-resistant pathogens should further be explored to identify the molecular mechanisms and synergistic/antagonistic effects with conventional antimicrobials. There were no studies on investigating eugenol's potential in in vivo infectious animal models. This is the first review on eugenol that details the antimicrobial potential of eugenol and its possible applications as a protectant in the food industry.