Safe and effective anticancer drug discovery is still a challenge for medicinal chemists. The fused polycyclic chemical features of the anthraquinone ring offer rigidity, planarity, and aromaticity suitable for DNA intercalation in cancer cells and bacterial cells. Several 2-hydroxyanthraquinone derivatives have been found to produce excellent antiproliferative effects on cancer and bacterial cells in vitro. Therefore, in this study, various quaternizable secondary and tertiary amines were substituted to 2-hydroxyanthraquinone to yield ethoxy anthraquinone derivatives 21a-d and 22a-d. These newly synthesized anthraquinone derivatives were evaluated for their antiproliferative properties against human breast cancer cell lines MCF-7 and MDA-MB-231. They were also evaluated for their probable in vitro antiproliferative effect on ESKAPE pathogens. The toxicity of the lead derivative 21d and 22a was evaluated on human peripheral blood mononuclear cells (PBMCs) using the MTT assay. The anthraquinone 13b, 13c, 14c, and 14b showed moderate anticancer activity with an IC50 value of-135 mu g/ mL against MCF-7 and MDA-MB-231 cell lines. Compounds 13c-d and 14a-d showed moderate to average antibacterial susceptibility. The in vitro toxicity study against PMBCs revealed that these derivatives are nontoxic. The in silico studies reveal that these derivatives have good drug-likeness, high oral absorption, and good binding affinities for MAP kinase p38 protein. Incorporation of a quaternizable amino function to the 2-hydroxyanthraquinone was found to be a promising approach to enhance the antiproliferative effects and overcome the toxicity-associated drawbacks of the anthraquinone ring.

Coumarin is an important heterocyclic molecular framework of bioactive molecules against broad spectrum pathological manifestations. In the present study 18 new coumarin derivatives (CDs) were synthesized and characterized for antibiofilm activity against two model bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa. It was observed that all the CDs executed significant effect in moderating activities against both planktonic and biofilm forms of these selected bacteria. Hence, to interpret the underlying probable reason of such antibiofilm effect, in-silico binding study of CDs with biofilm and motility associated proteins of these organisms were performed. All CDs have shown their propensity for occupying the native substrate binding pocket of each protein with moderate to strong binding affinities. One of the CDs such as CAMN1 showed highest binding affinity with these proteins. Interestingly, the findings of in-silico studies coincides the experimental results of antibiofilm and motility affect of CDs against both S. aureus and P. aeruginosa. Moreover, in-silico studies suggested that the antibiofilm activity of test CDs may be due to the interference of biofilm and motility associated proteins of the selected model organisms (PilT from P. aeruginosa and TarK, TarO from S. aureus). The detailed synthesis, characterization, methodology and results of biological screening along with computational studies have been reported. This study could be of greater interest in the context of the development of new anti-bacterial agent in the future.

In the quest for advancing bio-conjugated metal nanoparticle synthesis as a promising avenue in biochemistry, this study emphasizes the optimized fabrication of silver nanoparticles mediated by Spondias pinnata. The synthesized silver nanoparticles (SP-AgNPs) exhibited remarkable colloidal stability for 6-7 months at ambient temperature (25 ± 4 °C) supported by a highly negative zeta potential of -37 mV. Characterization via HR-TEM, XRD, XPS, ICP-OES, and DLS studies confirmed the spherical morphology of the SP-AgNPs, with an average diameter of 32 ± 5 nm and a face-centered cubic (fcc) arrangement of particles. The SP-AgNPs demonstrated significant antibacterial and antibiofilm activity against Escherichia coli (E. coli) MTCC 118 strain and catalytic dye degradation activity against methylene blue (MB). Notable antibacterial activity in planktonic growth assays with inhibition zones of 6.15 mm and 6.9 mm and 63.51% reduction in bacterial proliferation at concentrations of 150 µg/mL and 175 µg/mL, respectively were observed for SP-AgNps. At 175 µg/mL, biofilm formation was also suppressed by 55.55% along with a pronounced reduction in bacterial motility.In addition, SP-AgNPs facilitated a maximum of 86% dye degradation efficiency adhering to pseudo-first-order kinetics with a rate constant of 0.01991 min⁻¹.These findings underscore the potential of SP-AgNPs as multifunctional silver nanoparticles with promising applications in both biomedical and environmental domains.

In this study, biogenic silver nanoparticles (AgNPs) were successfully synthesized using the aqueous leaf extract of Spilanthes paniculata (SP) via an optimized green synthesis approach. The synthesized SP-AgNPs were characterized using SEM, TEM, EDAX, DLS, UV-vis, FTIR, XRD, and Zeta potential analysis. The results showed that the obtained silver nanoparticles (SP-AgNPs) were crystalline in nature and spherical in shape, with an average size of 17 nm (XRD). Additionally, SP-AgNPs exhibited significant antibacterial activity against both the planktonic and biofilm forms of Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA). Hemocompatibility assessment using sheep red blood cells (RBCs) indicated the nontoxic nature of SP-AgNPs. In addition, SP-AgNPs demonstrated significant antioxidant potential against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals, along with notable catalytic activity in the degradation of methylene blue, methyl violet, and methyl orange dyes. Collectively, this study on the biogenic synthesis of silver nanoparticles under optimized conditions, along with the comprehensive evaluation of their antibacterial, antioxidant, and catalytic properties, highlights the potential of SP as a sustainable biofactory for multifunctional nanomaterials. This study may thus serve as a valuable reference for future multidisciplinary research involving biogenic silver nanoparticles.

Anthraquinones are well known for their wide spectrum of pharmacological properties. Anthraquinone antibiotics, such as doxorubicin, daunorubicin, epirubicin, and mitoxantrone, have long been used in the clinical management of various tumors. However, their use is limited due to their toxicity effects, especially cardiomyopathy, despite their pronounced therapeutic effects. In recent years, medicinal chemists have explored the possibility of modifying the anthraquinone ring appended with structurally diverse functionality in order to develop better chemotherapeutic agents with fewer adverse effects. The fused polycyclic structure of anthraquinone offers rigidity, planarity, and aromaticity, which helps in double helix DNA intercalation, disruption of G4 DNA, and inhibition of topoisomerase-II enzyme of cancer cells, making them suitable pharmacophore for anticancer drug discovery. Incorporation of suitable functional groups such as amino, hydroxyl, and their derivatives into anthraquinone rings can improve their interactions with biological targets involved in cancer progression. These subtle structural changes produce newer anthraquinone derivatives with improved anticancer properties, increased potency, selectivity, and reduced toxicity, and can overcome multi-drug resistance. On the other hand, the molecular hybrids of the anthraquinone derivatives have been reported to act on multiple targets in cancer cells, as seen in the case of clinical candidates like alectinib, midostaurin, tucatinib, belinostat, and dacinostat. Molecular hybrid has given a new direction for anticancer drug development, which can produce bifunctional drug candidates with reduced toxicity. This review summarizes different structural modifications that have been made to the anthraquinone ring in the last decade with the aim of bringing out potent yet toxicity-free anticancer agents.

Over the past few years, organic small molecules (OSM) having a π-conjugated heteroatomic aromatic backbone along with terminal donor-acceptor (D-A) groups have emerged as one of the most promising materials for organic resistive switching (ORS) devices. In this research, the resistive switching (RS) properties of two rationally synthesized coumarin derivatives, 7-(2-(benzylamino)ethoxy)-4-methyl-2H-chromen-2-one (CAMN1) and 7-(2-(4-methoxyphenylamino)ethoxy)-4-methyl-2H-chromen-2-one (CAMN2), have been exhaustively studied. The CAMN1-based ORS device exhibited WORM RS behavior with an excellent device yield of 97.22%, while the CAMN2-based device showed both WORM as well as RRAM RS behavior depending on the compliance current (CC) with a perfect device yield of 100%. Both devices exhibited superior read endurance on the order of 104 as well as a retention time of at least 3 × 104 s with a very good memory window of the order of 104 or more. Moreover, both devices exhibited superior long-term physical and thermal stability. The cyclability of the CAMN2-based device in the RRAM mode of operation was found to be 116 cycles. DFT-based calculations as well as absorption spectroscopic studies reveal the role of the intra/intermolecular charge transfer (CT) in the RS behavior of both the devices. Moreover, the presence of the methoxy (-OCH3) group in the CAMN2 molecule has been identified as the key reason behind the observed difference in the RS behaviors of the two molecules.

Due to the unique color-changing properties of polydiacetylene (PDA), it has been extensively investigated for designing various types of chemo-sensors for the detection of different target analytes. In this article, we have explored the thermodynamic and structural characteristics of Langmuir monolayers formed by 10,12-heptacosadiynoic acid (HCDA), coumarin derivatives (MOCO), and their mixtures to tune PDA phases for demonstrating suitable sensing applications. Analysis of pressure-area (π − A) isotherms, excess area, and Gibbs free energy reveals that pure HCDA and its mixtures with MOCO exhibit significant variations in monolayer behavior, particularly in trilayer formation, which is crucial for polymerization. The results show that all the mixed monolayers display non-ideal mixing behavior, with positive excess area and Gibbs free energy indicating repulsive interactions. Whereas, at a 0.9 mole fraction of HCDA, the repulsion is less and mixing is closer to ideal behaviour. Compression modulus (Cs−1) analysis further explores the phase transitions of the PDA monolayers. Brewster Angle Microscopy (BAM) images provide visual confirmation of structural changes and polymerization under UV illumination. Spectroscopic characterization reveals that phase transitions from blue to red significantly influenced by the presence of MOCO. Additionally, the HCDA/MOCO mixed monolayers of 0.9 mole fraction of HCDA demonstrate enhanced sensitivity to volatile organic compounds (VOCs). This research demonstrates the potential of HCDA and its mixtures with MOCO in developing advanced PDA-based sensors for VOC detection.

During the past few years, a large number for organic small molecules (OSM) have been identified which may act as the active layer in resistive switching (RS) devices. In general, metal coated glass substrates are used as the bottom electrode in these devices which may contribute largely towards the global e-waste generation. This shortcoming may be addressed by utilizing paper substrate based non-metallic conductors like conductive polymers, graphene, graphite etc., In the present communication, we report a coumarin based RS device where a graphite-coated paper substrate has been utilized as the bottom electrode. The device exhibited write-once-read-many (WORM) type RS behaviour with an excellent memory window of the order of 104. Moreover, the read endurance and the data retention time of the device have been found to be 104 cycles and 2 h (measured), respectively. Furthermore, slope analysis of the I-V curve in double-logarithmic plot revealed that typical trap controlled SCLC mechanism is the key behind current conduction in the present device.

In this study, silver nanoparticles (PE-AgNPs) were synthesized using Premna esculenta (PE) leaf extract, characterized by UV, TEM, TEM-EDX, XRD, DLS, and ICPOES studies. AgNPs were found to be stable at -35 mV with 26.157 ppm concentration. AgNPs were found triangular in shape with an average size of about 44 nm. Hepatoprotective activity was assessed in animal model using silymarin as standard drug. Biochemical parameters (serum AST, ALT, gamma GT, ACP, and ALP), inflammatory markers (IL 1 beta, IL 17, TNF alpha, and IL 10), and antioxidant markers (GSH, SOD, Catalase, and LPO) were assayed. Liver tissue was processed for histological analysis. Induction of hepatotoxicity increases AST, ALT, gamma GT, ACP, ALP, IL 10, LPO, and decreases IL 1 beta, IL 17, TNF alpha, GSH, SOD, and Catalase. PE-AgNPs treatment significantly decreases IL 10, LPO while IL 1 beta, IL 17, TNF alpha, GSH, and SOD were increased in animals. PE-AgNPs partially recovered CCl4-induced changes in liver histology.

OBJECTIVES Oral squamous cell carcinoma (OSCC) is the predominant type of oral cancer. Its incidence is high in certain geographic regions, and it is correlated with chewing tobacco. Epidermal growth factor receptor (EGFR), induced by tobacco carcinogens, is overexpressed in OSCC, leading to poor prognosis. Thus, EGFR inhibitors are promising agents against OSCC. High cost and toxicity of existing EGFR inhibitors necessitate alternative EGFR-targeted therapy. Here, we tested the antitumor potential of ethyl acetate fraction of an ethnomedicinal tree, Oroxylum indicum stem bark extract (OIEA) in a 4-nitroquinoline-1-oxide (4NQO)-induced oral carcinogenesis model. METHODS OIEA was prepared by solvent extraction method, and subsequently its in vitro radical scavenging activities were measured. High-performance liquid chromatography (HPLC) analysis of OIEA was done to identify the constituent active compounds. Hemolytic, trypan blue exclusion, and MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide] assays were performed in normal and cancer cells to select an optimum dose of OIEA for antitumor activity study in 4NQO-induced oral cancer in F344 rats. Measurement of tumor volume, weight, and cell count was followed by tumor cell cycle analysis and comet and annexin V/Propidium Iodide (PI) assay. Pro-apoptotic markers were detected by western blot testing. Molecular docking was done to predict the interaction between OIEA active component and EGFR or phosphatidylinositol-3-kinase (PI3K), which was further validated biologically. Finally, hepatic and renal function testing and histopathology were performed. RESULTS OIEA reduced tumor burden and increased survivability of the tumor-bearing rats significantly as compared to untreated tumor bearers. HPLC revealed oroxylin A as the predominant bioactive component in OIEA. Molecular docking predicted significant binding between oroxylin A and EGFR as well as PI3K, which was confirmed by western blot analysis of in vivo samples. OIEA also ameliorated hepato-, renal- and myelotoxicity induced by 4NQO. CONCLUSION OIEA reduces 4NQO-induced OSCC by modulating the EGFR/PI3K/AKT signaling cascade and also ameliorated toxicity in tumor bearers.

The current Coronavirus Disease 2019 (COVID-19) pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is highly contagious infection that breaks the healthcare systems of several countries worldwide. Till to date, no effective antiviral drugs against COVID-19 infection have reached the market, and some repurposed drugs and vaccines are prescribed for the treatment and prevention of this disease. The currently prescribed COVID-19 vaccines are less effective against the newly emergent variants of concern of SARS-CoV-2 due to several mutations in viral spike protein and obviously there is an urgency to develop new antiviral drugs against this disease. In this review article, we systematically discussed the anti-SARS-CoV-2 and anti-inflammatory efficacy of two flavonoids, baicalein and its 7-O-glucuronide, baicalin, isolated from Scutellaria baicalensis, Oroxylum indicum, and other plants as well as their pharmacokinetics and oral bioavailability, for development of safe and effective drugs for COVID-19 treatment. Both baicalein and baicalin target the activities of viral S-, 3CL-, PL-, RdRp- and nsp13-proteins, and host mitochondrial OXPHOS for suppression of viral infection. Moreover, these compounds prevent sepsis-related inflammation and organ injury by modulation of host innate immune responses. Several nanoformulated and inclusion complexes of baicalein and baicalin have been reported to increase oral bioavailability, but their safety and efficacy in SARS-CoV-2-infected transgenic animals are not yet evaluated. Future studies on these compounds are required for use in clinical trials of COVID-19 patients.

Plant extracts have been used to treat microbiological diseases for centuries. This study examined plant triterpenoids tormentic acid (TA) and 23-hydroxycorosolic acid (HCA) for their antibiofilm effects on Staphylococcus aureus strains (MTCC-96 and MTCC-7405). Biofilms are bacterial colonies bound by a matrix of polysaccharides, proteins, and DNA, primarily impacting healthcare. As a result, ongoing research is being conducted worldwide to control and prevent biofilm formation. Our research showed that TA and HCA inhibit S. aureus planktonic growth by depolarizing the bacterial membrane. In addition, zone of inhibition studies confirmed their effectiveness, and crystal violet staining and biofilm protein quantification confirmed their ability to prevent biofilm formation. TA and HCA exhibited substantial reductions in biofilm formation for S. aureus (MTCC-96) by 54.85

Here, we report a simple, efficient, and green protocol for the one-pot synthesis of pyrano[2,3-c]pyrazole derivatives via a sequential three-component strategy using aromatic aldehydes, malononitrile and pyrazolin-5-one in a water-SDS-ionic liquid system. This is a base and volatile organic solvent-free approach that could be applicable to a wide substrate scope. The key advantages of the method over other established protocols are very high yield, eco-friendly conditions, chromatography-free purification and recyclability of the reaction medium. Our study revealed that the N-substituent present in pyrazolinone controls the selectivity of the process. N-unsubstituted pyrazolinone favours the formation of 2,4-dihydro pyrano[2,3-c]pyrazoles whereas under identical conditions N-phenyl substituent pyrazolinone favours the formation 1,4-dihydro pyrano[2,3-c]pyrazoles. Structures of the synthesized products were established by NMR and X-ray diffraction techniques. Energy optimized structures and energy gaps between the HOMO-LUMO of some selected compounds were estimated using density functional theory to explain the extra stability of the 2,4-dihydro pyrano[2,3-c]pyrazoles over 1,4-dihydro pyrano[2,3-c]pyrazoles.

The clinical use of anthraquinone antibiotics such as doxorubicin in cancer chemotherapy is limited due to their toxic cardiomyopathy effects. The conjugation of anthraquinones with fatty acids is known to enhance bioactivity by increasing lipophilicity and facilitating cell membrane permeation. Short-chain saturated fatty acids such as capric, caprylic, caproic acids, and lauric acids are known for their inherent anticancer properties on human colorectal cancer cells. In this study, 2-hydroxyanthraquinone and saturated fatty acid esters were synthesized and evaluated against human colon cancer cell line HT-29 and Colo-205, breast cancer cell lines MDA-MB-231 and MCF-7, and leukemia cell line K-562 for their in vitro anticancer properties using a sulforhodamine B (SRB) assay. The anthraquinone-saturated fatty acid conjugates produced excellent activity against human colon and breast cancer cell lines. The octanoic acid and hexanoic acid derivatives of 2-hydroxy anthraquinone showed excellent anticancer activity with GI(50) values of 0.2 nM and 1.0 nM against human colon cancer cell line Colo-205 and the human breast cancer cell line MCF-7, respectively, and emerged as the most active compounds. Furthermore, the in vitro cytotoxicity study against peripheral blood mononuclear cells showed that these derivatives are non-toxic in nature.

Bis-coumarins are distinguished derivatives of coumarin which bear numerous pharmaceutical and other applications. In continuation of our ongoing research towards the development of benign protocols for various heterocyclic systems, herein we report an Amberlyst 15 mediated synthesis of unsymmetrical bis-coumarins via in situ generation and cyclization of symmetrical bis-coumarinyl methanes derived from o-hydroxy aromatic aldehydes and 4-hydroxy coumarin. Aldehydes of both electron-donating and electron-withdrawing units underwent smooth conversion to their respective unsymmetrical bis-coumarins (76-98 % yield) without leaving any side products or intermediates. The catalyst used in the present protocol is cost-effective, eco-friendly, and readily available which could be recovered and reused several times. This methodology offers operational simplicity, low catalyst loading, and avoids the use of toxic solvents/reagents and the product can be isolated without chromatography. DFT study indicated that the driving force for the cyclisation of symmetrical bis-coumarin is the minimization of the tetrahedral bond angle deviations along with other small non-covalent interactions. Some DFT data was also verified with the data obtained from the X-rays crystallographic study. Here, we report a simple and efficient protocol for the synthesis of unsymmetrical bis-coumarins from 4-hydroxy coumarin and 2-hydroxy araldehydes in the presence of Amberlyst 15 through the condensation-addition-cyclodehydration processimage

Cell Surface hydrophobicity is one of the determinant biophysical parameters of bacterial aggregation for being networked to form a biofilm. Phytoconstituent, like vitexin, has long been in use for their antibacterial effect. The present work demonstrates the role of vitexin in modulating Staphylococcus aureus surface hydrophobicity while aggregating to form biofilm and pathogenesis in a host. In planktonic form, vitexin shows minimum inhibitory concentration at 252 µg/ml against S. aureus. Sub-MIC doses of vitexin and antibiotics (26 µg/ml of vitexin, 55 µg/ml of azithromycin, and 2.5 µg/ml of gentamicin) were selected to treat S. aureus. Dead cell counts after treatment were studied through flow cytometry. As dead cell counts were minimal (<5 %), these doses were considered for all subsequent experiments. While studying aggregating cells, it was observed that vitexin reduces S. aureus surface hydrophobicity and membrane permeability at the sub-MIC dose of 26 µg/ml. The in silico binding analysis showed a higher binding affinity of vitexin with surface proteins (IcaA, DltA, and SasG) of S. aureus. Down-regulation of dltA and icaAB expression, along with the reduction in membrane potential with a sub-MIC dose of vitexin, explains reduced S. aureus surface hydrophobicity. Vitexin was found to interfere with S. aureus biofilm-associated protein biomass, EPS production, and swarming movement. Subsequently, the suppression of proteases production and down-regulation of icaAB and agrAC gene expression with a sub-MIC dose of vitexin explained the inhibition of S. aureus virulence in vitro. Besides, vitexin was also found to potentiate the antibiofilm activity of sub-MIC doses of gentamicin and azithromycin. Treatment with vitexin exhibits a protective response in S. aureus infected macrophages through modulation of expression of cytokines like IL-10 and IL-12p40 at protein and mRNA levels. Furthermore, CFU count and histological examination of infected mouse tissue (liver and spleen) justify the in vivo protective effect of vitexin from S. aureus biofilm-associated infection. From this study, it can be inferred that vitexin can reduce S. aureus surface hydrophobicity, leading to interference with aggregation at the time of biofilm formation and subsequent pathogenesis in a host.

A dehydrogenative coupling of N ‐uracil amidines with (hetero)aryl methanols has been developed, allowing for the facile synthesis of a broad range of structurally diverse pyrimidouracils. By applying [RuCl 2 ( p ‐cymene)] 2 /Cs 2 CO 3 as an efficient catalytic system, the easily available, cheap (hetero)aryl methanols were firstly employed for oxidative insertion/CH amination into the N ‐uracil amidines, providing highly functionalized pyrimido[4,5‐ d ]pyrimidine‐2,4‐diones. Due to the better stability of alcohols than aldehydes, this synthetic protocol is applicable to a broad range of alcoholic substrates and does not required any protection during the whole preparation process. The presented protocol has the potential to prepare valuable products which cannot be accessed presently or extremely arduous to procure by following regular procedure. Hence, this is a remarkably improved protocol compared with the existing methodologies. The overall reaction sequence is an effective oxidation‐imination‐cyclization tandem process catalyzed by ruthenium catalyst.