Biogenic Silver Nanoparticles/Mg-Al Layered Double Hydroxides with Peroxidase-like Activity for Mercury Detection and Antibacterial Activity.

Over the past decade, the attention of researchers has been drawn to materials with enzyme-like properties to substitute natural enzymes. The ability of nanomaterials to mimic enzymes makes them excellent enzyme mimics; nevertheless, there is a wide berth for improving their activity and providing a platform to heighten their potential. Herein, we report a green and facile route for Tectona grandis leaves extract-assisted synthesis of silver nanoparticles (Ag NPs) decorated on Mg-Al layered double hydroxides (Mg-Al-OH@TGLE-AgNPs) as a nanocatalyst. The Mg-Al-OH@TGLE-AgNPs nanocatalyst was well characterized, and the average crystallite size of the Ag NPs was found to be 7.92 nm. The peroxidase-like activity in the oxidation of o-phenylenediamine in the presence of H2O2 was found to be an intrinsic property of the Mg-Al-OH@TGLE-AgNPs nanocatalyst. In addition, the use of the Mg-Al-OH@TGLE-AgNPs nanocatalyst was extended towards the quantification of Hg2+ ions which showed a wide linearity in the concentration range of 80-400 µM with a limit of detection of 0.2 nM. Additionally, the synergistic medicinal property of Ag NPs and the phytochemicals present in the Tectona grandis leaves extract demonstrated notable antibacterial activity for the Mg-Al-OH@TGLE-AgNPs nanocatalyst against Gram-negative Escherichia coli and Gram-positive Bacillus cereus.

Palladium Nanoparticles Grafted onto Phytochemical Functionalized Biochar: A Sustainable Nanozyme for Colorimetric Sensing of Glucose and Glutathione.

The devising and development of numerous enzyme mimics, particularly nanoparticles and nanomaterials (nanozymes), have been sparked by the inherent limitations imposed by natural enzymes. Peroxidase is one of the enzymes that is extensively utilized in commercial, medical, and biological applications because of its outstanding substrate selectivity. Herein, we present palladium nanoparticles grafted on Artocarpus heterophyllus (jackfruit) seed-derived biochar (BC-AHE@Pd) as a novel nanozyme to imitate peroxidase activity en route to the rapid and colorimetric detection of H2O2, exploiting o-phenylenediamine as a peroxidase substrate. The biogenically generated BC-AHE@Pd nanocatalyst was synthesized utilizing Artocarpus heterophyllus seed extract as the reducing agent for nanoparticle formation, while the residue became the source for biochar. Various analytical techniques like FT-IR, GC-MS, FE-SEM, EDS, TEM, SAED pattern, p-XRD, and ICP-OES, were used to characterize the BC-AHE@Pd nanocatalyst. The intrinsic peroxidase-like activity of the BC-AHE@Pd nanocatalyst was extended as a prospective nanosensor for the estimation of the biomolecules glucose and glutathione. Moreover, the BC-AHE@Pd nanocatalyst showed recyclability up to three recycles without any significant loss in activity.

Synthesis, molecular docking studies, and in vitro antimicrobial evaluation of piperazine and triazolo-pyrazine derivatives.

For this work, two series of new piperazine derivatives (3a-o) and triazolo-pyrazine derivatives (3p-t) were synthesized in a single-step reaction. All twenty adducts were obtained in good to high yields and fully characterized by 1H NMR, 13C NMR, IR, and mass spectrometry techniques. To further confirm the chemical identity of the adducts, a crystal of N-{[(4-chlorophenyl)-3-(trifluoromethyl)]-5,6-dihydro-[1,2,4]triazolo[4,3-a]}pyrazine-7(8H)-carboxamide (3t) was prepared and analyzed using X-ray crystallography. In vitro screening of the antimicrobial activity of all compounds (3a-t) was evaluated against five bacterial and two fungal strains. This study disclosed that N-{[(3-chlorophenyl)]-4-(dibenzo[b,f][1,4]thiazepin-11-yl)}piperazine-1-carboxamide (3o) was the superior antimicrobial with good growth inhibition against A. baumannii. Furthermore, the results from the performed molecular docking studies were promising, since the observed data could be used to develop more potent antimicrobials.

Carbazole Derivatives as Potential Antimicrobial Agents.

Microbial infection is a leading cause of death worldwide, resulting in around 1.2 million deaths annually. Due to this, medicinal chemists are continuously searching for new or improved alternatives to combat microbial infections. Among many nitrogen-containing heterocycles, carbazole derivatives have shown significant biological activities, of which its antimicrobial and antifungal activities are the most studied. In this review, miscellaneous carbazole derivatives and their antimicrobial activity are discussed (articles published from 1999 to 2022).

Comprehensive Review on Medicinal Applications of Coumarin-Derived Imine-Metal Complexes.

Coumarins are fused six-membered oxygen-containing benzoheterocycles that join two synthetically useful rings: α-pyrone and benzene. A survey of the literature shows that coumarins and their metal complexes have received great interest from synthetic chemists, medicinal scientists, and pharmacists due to their wide spectrum of biological applications. For instance, coumarin and its derivatives have been used as precursors to prepare a large variety of medicinal agents. Likewise, coumarin-derived imine-metal complexes have been found to display a variety of therapeutic applications, such as antibacterial, antifungal, anticancer, antioxidant, anthelmintic, pesticidal, and nematocidal activities. This review highlights the current synthetic methodologies and known bioactivities of coumarin-derived imine-metal complexes that make this molecule a more attractive scaffold for the discovery of newer drugs.

Efficient and recyclable palladium enriched magnetic nanocatalyst for reduction of toxic environmental pollutants.

In this paper, highly stable, powerful, and recyclable magnetic nanoparticles tethered N-heterocyclic carbene-palladium(II) ((CH3)3-NHC-Pd@Fe3O4) as magnetic nanocatalyst was successfully synthesized from a simplistic multistep synthesis under aerobic conditions through easily available low-cost chemicals. Newly synthesized (CH3)3-NHC-Pd@Fe3O4 magnetic nanocatalyst was characterized from various analytical tools and catalytic potential of the (CH3)3-NHC-Pd@Fe3O4 magnetic nanocatalyst was studied for the catalytic reduction of toxic 4-nitrophenol (4-NP), hexavalent chromium (Cr(VI)), Methylene Blue (MB) and Methyl Orange (MO) at room temperature in aqueous media. UV-Visible spectroscopy was employed to monitor the reduction reactions. New (CH3)3-NHC-Pd@Fe3O4 magnetic nanocatalyst exhibited excellent catalytic activity for the reduction of toxic environmental pollutants. Moreover, (CH3)3-NHC-Pd@Fe3O4 magnetic nanocatalyst could be easily and rapidly separated from the reaction mixture with the help of an external magnet and recycled minimum five times in reduction of 4-NP, MB, MO and four times in Cr(VI) without significant loss of catalytic potential and remains stable even after reuse.

Design, synthesis, and molecular docking study of new piperazine derivative as potential antimicrobial agents.

Herein, we describe the successful design and synthesis of seventeen new 1,4-diazinanes, compounds commonly known as piperazines. This group of piperazine derivatives (3a-q) were fully characterized by 1H NMR, 13C NMR, FT-IR, and LCMS spectral techniques. The molecular structure of piperazine derivative (3h) was further established by single crystal X-ray diffraction analysis. All reported compounds were evaluated for their antibacterial and antifungal potential against five bacterial (Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa) and two fungal strains (Candida albicans and Cryptococcus neoformans). The complete bacterial screening results are provided. As documented, piperazine derivative 3e performed the best against these bacteria. Additionally, data obtained during molecular docking studies are very encouraging with respect to potential utilization of these compounds to help overcome microbe resistance to pharmaceutical drugs, as explicitly noted in this manuscript.

Synthesis, molecular docking studies, and antimicrobial evaluation of new structurally diverse ureas.

A series of new urea derivatives (3a-p) have been synthesized from readily available isocyanates and amines in good to high yields. All synthesized compounds were fully characterized using 1H NMR, 13C NMR, IR, and mass spectrometry. Additionally, the structure of the compound (3n) was confirmed by single-crystal X-ray diffraction. Furthermore, all compounds were evaluated for antimicrobial activity against five bacteria and two fungi. Last but not the least, molecular docking studies with Candida albicans dihydropteroate synthetase were performed and the results are presented herein.

Identification of Novel Bisbenzimidazole Derivatives as Anticancer Vacuolar (H⁺)-ATPase Inhibitors.

The vacuolar (H⁺)-ATPases (V-ATPases) are a family of ATP-driven proton pumps and they have been associated with cancer invasion, metastasis, and drug resistance. Despite the clear involvement of V-ATPases in cancer, the therapeutic use of V-ATPase-targeting small molecules has not reached human clinical trials to date. Thus, V-ATPases are emerging as important targets for the identification of potential novel therapeutic agents. We identified a bisbenzimidazole derivative (V) as an initial hit from a similarity search using four known V-ATPase inhibitors (I-IV). Based on the initial hit (V), we designed and synthesized a focused set of novel bisbenzimidazole analogs (2a-e). All newly prepared compounds have been screened for selected human breast cancer (MDA-MB-468, MDA-MB-231, and MCF7) and ovarian cancer (A2780, Cis-A2780, and PA-1) cell lines, along with the normal breast epithelial cell line, MCF10A. The bisbenzimidazole derivative (2e) is active against all cell lines tested. Remarkably, it demonstrated high cytotoxicity against the triple-negative breast cancer (TNBC) cell line, MDA-MB-468 (IC50 = 0.04 ± 0.02 µM). Additionally, it has been shown to inhibit the V-ATPase pump that is mainly responsible for acidification. To the best of our knowledge the bisbenzimidazole pharmacophore has been identified as the first V-ATPase inhibitor in its class. These results strongly suggest that the compound 2e could be further developed as a potential anticancer V-ATPase inhibitor for breast cancer treatment.

Design, Synthesis and Biological Evaluation of Novel 5H-Chromenopyridines as Potential Anti-Cancer Agents.

A novel series of 5H-chromenopyridines was identified as anticancer agents in our continuing effort to discover and develop new small molecule anti-proliferative agents. Based on our initial lead SP-6-27 compound, we designed and synthesized novel tricyclic 5H-thiochromenopyridine and 5H-chromenopyridine analogs to evaluate the impact of an additional ring, as well as conformational flexibility on cytotoxic activity against human melanoma and glioma cell lines. All of the 5H-thiochromenopyridines have been achieved in good yields (89%-93%) using a single-step, three-component cyclization without the need for purification. The 5H-chromenopyridine analog of the potent 5H-thiochromenopyride was obtained in a good yield upon purification. All newly-prepared 5H-thiochromenopyridines showed good to moderate cytotoxicity against three melanoma and two glioma cell lines (3-15 µM). However, the 5H-chromenopyridine analogue that we prepared in our laboratory lost cytotoxic activity. The moderate cytotoxic activity of 5H-thiochromenopyridines shows the promise of developing chromenopyridines as potential anticancer agents.

Cerebrovascular dilation via selective targeting of the cholane steroid-recognition site in the BK channel ß1-subunit by a novel nonsteroidal agent.

The Ca(2+)/voltage-gated K(+) large conductance (BK) channel ß1 subunit is particularly abundant in vascular smooth muscle. By determining their phenotype, BK ß1 allows the BK channels to reduce myogenic tone, facilitating vasodilation. The endogenous steroid lithocholic acid (LCA) dilates cerebral arteries via BK channel activation, which requires recognition by a BK ß1 site that includes Thr169. Whether exogenous nonsteroidal agents can access this site to selectively activate ß1-containing BK channels and evoke vasodilation remain unknown. We performed a chemical structure database similarity search using LCA as a template, along with a two-step reaction to generate sodium 3-hydroxyolean-12-en-30-oate (HENA). HENA activated the BK (cbv1 + ß1) channels cloned from rat cerebral artery myocytes with a potency (EC50 = 53 µM) similar to and an efficacy (×2.5 potentiation) significantly greater than that of LCA. This HENA action was replicated on native channels in rat cerebral artery myocytes. HENA failed to activate the channels made of cbv1 + ß2, ß3, ß4, or ß1T169A, indicating that this drug selectively targets ß1-containing BK channels via the BK ß1 steroid-sensing site. HENA (3-45 µM) dilated the rat and C57BL/6 mouse pressurized cerebral arteries. Consistent with the electrophysiologic results, this effect was larger than that of LCA. HENA failed to dilate the arteries from the KCNMB1 knockout mouse, underscoring BK ß1's role in HENA action. Finally, carotid artery-infusion of HENA (45 µM) dilated the pial cerebral arterioles via selective BK-channel targeting. In conclusion, we have identified for the first time a nonsteroidal agent that selectively activates ß1-containing BK channels by targeting the steroid-sensing site in BK ß1, rendering vasodilation.

Advances in the synthesis and applications of 2D MXene-metal nanomaterials.

MXenes, two-dimensional (2D) materials that consist of transition metal carbides, nitrides and/or carbonitrides, have recently attracted much attention in energy-related and biomedicine fields. These materials have substantial advantages over traditional carbon graphenes: they possess high conductivity, high strength, excellent chemical and mechanical stability, and superior hydrophilic properties. Furthermore, diverse functional groups such as -OH, -O, and -F located on the surface of MXenes aid the immobilization of numerous noble metal nanoparticles (NP). Therefore, 2D MXene composite materials have become an important and convenient option of being applied as support materials in many fields. In this review, the advances in the synthesis (including morphology studies, characterization, physicochemical properties) and applications of the currently known 2D MXene-metal (Pd, Ag, Au, and Cu) nanomaterials are summarized based on critical analysis of the literature in this field. Importantly, the current state of the art, challenges, and the potential for future research on broad applications of MXene-metal nanomaterials have been discussed.

Coumarin Triazoles as Potential Antimicrobial Agents.

Currently, in hospitals and community health centers, microbial infections are highly common diseases and are a leading cause of death worldwide. Antibiotics are generally used to fight microbial infections; however, because of the abuse of antibiotics, microbes have become increasingly more resistant to most of them. Therefore, medicinal chemists are constantly searching for new or improved alternatives to combat microbial infections. Coumarin triazole derivatives displayed a variety of therapeutic applications, such as antimicrobial, antioxidant, and anticancer activities. This review summarizes the advances of coumarin triazole derivatives as potential antimicrobial agents covering articles published from 2006 to 2022.

EDL-291, a novel isoquinoline, presents antiglioblastoma effects in vitro and in vivo.

To investigate the effectiveness of EDL-291, a 6,7-dimethoxy-1-[4-(4-methoxypyridin-3-yl)benzyl]-1,2,3,4-tetrahydroisoquinoline dihydrochloride compound, in inhibiting the survival of glioblastoma in vitro and in vivo. Dose-response curves were generated to determine the EC50 in rat and human glioblastoma cell lines by treatment with different dilutions of EDL-291. To evaluate the architecture of the glioblastoma cells after treatment with EDL-291, the rat and human glioblastoma cells were stained with Mito Tracker Green FM. To determine whether autophagy was induced in EDL-291-treated glioblastoma cells, both rat and human glioblastoma cell lines were stained with acridine orange and light chain-3 immunoblots were performed. The efficacy of EDL-291 was monitored in vivo using a rat glioblastoma model. Rat glioblastoma cells were transplanted into an intracranial rat model, followed by infusions of saline, a low dose of EDL-291 (20 mg/kg for the first half hour, followed by 40 mg/kg EDL-291 in saline for 4 h), or a high dose of EDL-291 (60 mg/kg for the first half hour, followed by 90 mg/kg EDL-291 for 4 h). EDL-291 inhibits glioblastoma in vitro by destroying the mitochondria as shown with Mito Tracker Green FM. Acridine orange staining and light chain-3 immunoblots suggest that autophagy is induced when glioblastoma cells are treated with EDL-291. In vivo, a low dosage of EDL-291 is sufficient and effective in reducing glioblastoma tumor size. EDL-291 selectively induces cell death in rat and human glioblastoma cell lines by the induction of autophagy. EDL-291 exhibits antiglioblastoma effects both in vitro and in vivo.

New substituted 4H-chromenes as anticancer agents.

As a continuation of our efforts to discover and develop small molecules as anticancer agents, we identified GRI-394837 as an initial hit from similarity search on RGD and its analogs. Based on GRI-394837, we designed and synthesized a focused set of novel chromenes (4a-e) in a single step using microwave method. All five compounds showed activity in the nanomolar range (IC(50): 7.4-640 nM) in two melanoma, three prostate and four glioma cancer cell lines. The chromene 4e is active against all the cell lines and particularly against the A172 human glioma cell line (IC(50): 7.4 nM). Interestingly, in vitro tubulin polymerization assay shows 4e to be a weak tubulin polymerization inhibitor but it shows very strong cytotoxicity in cellular assays, therefore there must be additional unknown mechanism(s) for the anticancer activity. Additionally, the strong antiproliferative activity was verified by one of the selected chromene (4a) by the NCI 60 cell line screen. These results strongly suggest that the novel chromenes could be further developed as a potential therapeutic agent for a variety of aggressive cancers.

Citrate transporter inhibitors: possible new anticancer agents.

The culmination of 80+ years of cancer research implicates the aberrant metabolism in tumor cells as a root cause of pathogenesis. Citrate is an essential molecule in intermediary metabolism, and its amplified availability to critical pathways in cancer cells via citrate transporters confers a high rate of cancer cell growth and proliferation. Inhibiting the plasma membrane and mitochondrial citrate transporters - whether individually, in combination, or partnered with complementary metabolic targets - in order to combat cancer may prove to be a consequential chemotherapeutic strategy. This review aims to summarize the use of different classes of citrate transporter inhibitors for anticancer activity, either individually or as part of a cocktail.

N-heterocyclic carbene metal complexes as therapeutic agents: a patent review.

INTRODUCTION: Besides the well-established catalytic, synthetic and materials related applications of N-heterocyclic carbene (NHC) metal complexes, their use as therapeutics deserves a special attention. Many literature reports indicate that their bioactivity is superior to other organometallic compounds. The main focus of patent disclosures in this area is the elucidation of anticancer and antimicrobial activities of NHC transition metal complexes. Nonetheless, a variety of other biological activities have been reported in non-patent literature to date. AREA COVERED: Patent literature on NHC metal complexes with focus on their therapeutic applications and relationship structure-biological activity disclosed since the first issued patent (2010) up to now (2021). The information was collected from publicly available data sources (e.g. Chemical Abstracts, MedLine, Reaxys, and SciFinder). EXPERT OPINION: Although the first reports on biological applications of NHC metal complexes originate in 2000s, the greatest progress in this area was made only in the past decade. A growing number of patent disclosures indicates that structural design of new NHC metal complexes is crucial for their successful use in both medicine and biochemistry. In the next few years, we expect to see more stable and effective NHC metal complexes as potential therapeutic agents and perhaps in clinical trials.

Medicinal applications of coumarins bearing azetidinone and thiazolidinone moieties.

Coumarins (2H-chromen-2-ones), also known as benzopyran-2-ones, are a family of naturally occurring heterocyclic ring systems that contain a lactone moiety. Coumarins exhibit a wide range of well-studied pharmacological properties. Over the last few decades, as a result of advances in diverse oriented synthetic routes, physicochemical properties and numerous biological activities, coumarins have become globally studied molecules from various synthetic and medicinal chemists. Recently, several bioactive coumarins bearing azetidinone and thiazolidinone moieties have been found to display a range of therapeutic characteristics, including antimicrobial, anticancer, antidiabetic and anti-inflammatory properties. This review offers a brief description of the synthetic methodologies, known bioactivity and structure-activity relationships of coumarins bearing azetidinones and thiazolidinones.

Exploration of (hetero)aryl Derived Thienylchalcones for Antiviral and Anticancer Activities.

BACKGROUND: Search for new antiviral and anticancer agents are essential because of the emergence of drug resistance in recent years. In continuation of our efforts in identifying the new small molecule antiviral and anticancer agents, we identified chalcones as potent antiviral and anticancer agents. OBJECTIVE: With the aim of identifying the broad acting antiviral and anticancer agents, we discovered substituted aryl/heteroaryl derived thienyl chalcones as antiviral and anticancer agents. METHOD: A focused set of thienyl chalcone derivaties II-VI was screened for selected viruses Hepatitis B virus (HBV), Herpes simplex virus 1 (HSV-1), Human cytomegalovirus (HCMV), Dengue virus 2 (DENV2), Influenza A (H1N1) virus, MERS coronavirus, Poliovirus 1 (PV 1), Rift Valley fever (RVF), Tacaribe virus (TCRV), Venezuelan equine encephalitis virus (VEE) and Zika virus (ZIKV) using the National Institute of Allergy and Infectious Diseases (NIAID)'s Division of Microbiology and Infectious Diseases (DMID) antiviral screening program. Additionally, a cyclopropylquinoline derivative IV has been screened for 60 human cancer cell lines using the Development Therapeutics Program (DTP) of NCI. RESULTS: All thienyl chalcone derivatives II-VI displayed moderate to excellent antiviral activity towards several viruses tested. Compounds V and VI were turned out be active compounds towards human cytomegalovirus for both normal strain (AD169) as well as resistant isolate (GDGr K17). Particularly, cyano derivative V showed very high potency (EC50: <0.05 µM) towards AD169 strain of HCMV compared to standard drug Ganciclovir (EC50: 0.12 µM). Additionally, it showed moderate activity in the secondary assay (AD169; EC50: 2.30 µM). The cyclopropylquinoline derivative IV displayed high potency towards Rift Valley fever virus (RVFV) and Tacaribe virus (TCRV) towards Rift Valley fever virus (RVFV). The cyclopropylquinoline derivative IV is nearly 28 times more potent in our initial in vitro visual assay (EC50: 0.39 µg/ml) and nearly 17 times more potent in neutral red assay (EC50: 0.71 µg/ml) compared to the standard drug Ribavirin (EC50: 11 µg/ml; visual assay and EC50: 12 µg/ml; neutral red assay). It is nearly 12 times more potent in our initial in vitro visual assay (EC50: >1 µg/ml) and nearly 8 times more potent in neutral red assay (EC50: >1.3 µg/ml) compared to the standard drug Ribavirin (EC50: 12 µg/ml; visual assay and EC50: 9.9 µg/ml; neutral red assay) towards Tacaribe virus (TCRV). Additionally, cyclopropylquinoline derivative IV has shown strong growth inhibitory activity towards three major cancers (colon, breast, and leukemia) cell lines and moderate growth inhibition shown towards other cancer cell lines screened. CONCLUSION: Compounds V and VI were demonstrated viral inhibition towards Human cytomegalovirus, whereas cyclopropylquinoline derivative IV towards Rift Valley fever virus and Tacaribe virus. Additionally, cyclopropylquinoline derivative IV has displayed very good cytotoxicity against colon, breast and leukemia cell lines in vitro.

New Urea Derivatives as Potential Antimicrobial Agents: Synthesis, Biological Evaluation, and Molecular Docking Studies.

A series of new urea derivatives, containing aryl moieties as potential antimicrobial agents, were designed, synthesized, and characterized by 1H NMR, 13C NMR, FT-IR, and LCMS spectral techniques. All newly synthesized compounds were screened in vitro against five bacterial strains (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Staphylococcus aureus) and two fungal strains (Candida albicans and Cryptococcus neoformans). Variable levels of interaction were observed for these urea derivatives. However, and of major importance, many of these molecules exhibited promising growth inhibition against Acinetobacter baumannii. In particular, to our delight, the adamantyl urea adduct 3l demonstrated outstanding growth inhibition (94.5%) towards Acinetobacter baumannii. In light of this discovery, molecular docking studies were performed in order to elucidate the binding interaction mechanisms of the most active compounds, as reported herein.