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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.

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.

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.

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.