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Mass movements and delta collapses are significant sources of tsunamis in lacustrine environments, impacting human societies enormously. Paleotsunamis studies play an essential role in understanding historical events and their consequences, along with their return periods. This study investigates a paleotsunami induced by a subaqueous mass movement during the Younger Dryas to Early Holocene transition, ca. 11,700 years ago in Lake Aiguebelette (NW Alps, France). Utilizing high‐resolution seismic and bathymetric surveys associated with sedimentological, geochemical, and magnetic analyses, we uncovered a paleotsunami triggered by a seismically induced mass transport deposit. Numerical simulations of mass movement have been conducted using a visco‐plastic Herschel‐Bulkley rheological model and corresponding tsunami wave modeled with dispersive and nondispersive models. Our findings reveal for the first time that dispersive effects may be negligible for subaqueous landslides in a relatively small lake. This research reconstructs a previously unreported paleotsunami event and enhances our understanding of tsunami dynamics in lacustrine environments. Plain Language Summary: This study explores an ancient landslide and its ability to potentially generate a tsunami. This event took place in Lake Aiguebelette, located in the NW Alps, France. By applying advanced underwater mapping techniques and computer modeling, we were able to reconstruct the origins and impact of this underwater prehistoric landslide. Our work revealed that this underwater landslide may have triggered a significant tsunami wave. These findings are crucial as they provide new insights into the dynamics of such geological events in lake environments, enhancing our understanding of their potential impacts and aiding in the preparation for future similar hazards. Key Points: Uncovered a 11,700‐year‐old subaqueous landslide‐induced paleotsunami in Lake Aiguebelette (NW Alps, France)Numerical model is constrained to reproduce the available geological dataFound dispersion effects to be of minimal importance in the modeling of this historical tsunami event [ABSTRACT FROM AUTHOR]

A low temperature hydrogen borrowing approach to generate secondary amines using benzimidazole-based N-heterocyclic carbene (BNHC) ruthenium complexes is reported. A series of the piano-stool complexes of the type [(η6-p-cymene)(BNHC)RuCl2] (1a-g) were synthesized via one-pot reaction of the NHC salt precursor, Ag2O, and [RuCl2(p-cymene)]2 and characterized using conventional spectroscopic techniques. The geometry of two precursors, [(η6-p-cymene)(Me4BnMe2BNHCCH2OxMe)RuCl2] (1f) and [(η6-pcymene)(Me5BnMe2BNHCCH2OxMe)RuCl2] (1g), was studied by single crystal X-ray diffraction. These catalysts were found to dehydrogenate alcohols efficiently at temperatures as low as 50 °C to allow Schiff-base condensation and subsequent imine hydrogenation to afford secondary amines. Notably, this ruthenium-based procedure enables the N-alkylation of aromatic and heteroaromatic primary amines with a wide range of primary alcohols in excellent yields of up to 98%. The present methodology is green and water is liberated as the sole byproduct. [ABSTRACT FROM AUTHOR]

Cancer is a complex multifactorial process, unchecked and abrupt division, and cell growth—conventional chemotherapy, along with radiotherapy, is used to treat breast cancer. Due to reduce efficacy and less survival rate, there is a particular need for the discovery of new active anticancer agents. Natural resources such as terrestrial/marine plants or organisms are a promising source for the generation of new therapeutics with improving efficacy. The screening of natural plant extracts and fractions, isolations of phytochemicals, and mechanistic study of those potential compounds play a remarkable role in the development of new therapeutic drugs with increased efficacy. Cancer is a multistage disease with complex signaling cascades. The initial study of screening whole extracts or fractions and later the isolation of secondary compounds and their mechanism of action study gives a clue of potential therapeutic agents for future drug development. The phytochemicals present in extracts/fractions produce remarkable effects due to synergistically targeting multiple signals. In this review, the molecular targets of extracts/ fractions and isolated compounds highlighted. The therapeutic agent's mechanistic targets in drug development focused involves; i) Induction of Apoptosis, ii) modulating cell cycle arrest, iii) Inhibition or suppression of invasion and metastasis and iv) various other pro-survival signaling pathways. The phytochemicals and their modified analogs identified as future potential candidates for anticancer chemotherapy. [ABSTRACT FROM AUTHOR]

Cancer is a complex mechanism involving a series of cellular events. The glycoproteins such as hyaluronan (HA) are a significant element of extracellular matrix (ECM), involve in the onset of cancer developmental process. The pivotal roles of HA in cancer progression depend on dysregulated expression in various cancer. HA, also gain attention due to consideration as a primary ligand of CD44 receptor. The CD44, complex transmembrane receptor protein, due to alternative splicing in the transcription process, various CD44 isoforms predominantly exist. The overexpression of distinct CD44 isoforms (CD44v) standard (CD44s) depends on the tumour type and stage. The receptor proteins, CD44 engage in a variety of biological processes, including cell growth, apoptosis, migration, and angiogenesis. HA-CD44 interaction trigger survival pathways that result in cell proliferation, invasion ultimately complex metastasis. The interaction and binding of ligand-receptor HA-CD44 regulate the downstream cytoskeleton pathways involve in cell survival or cell death. Thus, targeting HA, CD44 (variant and standard) isoform, and HA-CD44 binding consider as an attractive and useful approach towards cancer therapeutics. The use of various inhibitors of HA, hyaluronidases (HYALs), and utilizing targeted Nano-delivery of anticancer agents and antibodies against CD44, peptides gives promising results in vitro and in vivo. However, they are in clinical trials with favourable and unfavourable outcomes, which reflects the need for various modifications in targeting agents and a better understanding of potential targets in tumour progression pathways. [ABSTRACT FROM AUTHOR]

The present study was carried out to determine the effect of plant extract of Syzygium cumini and their silver nanoparticles (AgNPs) against the poultry pathogens. The plant extract was prepared in methanol, ethanol, ethyl acetate, chloroform, and n‐hexane. The results of phytochemical screening showed that the leaf extract of S. cumini have medicinally important phytochemical constituents. In the present study, AgNPs were synthesised by using an extract of S. cumini. Synthesised AgNPs were confirmed by Fourier‐transform infrared spectroscopy, ultraviolet–visible, and scanning electron microscopy. A surface plasmon resonance peak in absorption spectra showed absorption at 419 nm. The synthesised nanoparticles were found spherical in shape with the diameter range of 30–120 nm. The antimicrobial activity of crude extract and AgNPs was checked against the poultry bacterial pathogens by the agar well diffusion method. The authors' findings revealed that the crude extract and AgNPs have promising activities against all the test pathogens. It is concluded that the bioactive compounds from the extract of S. cumini and extract‐mediated AgNPs can be significantly used as an alternate poultry medicine to replace the available antibiotics, which have adverse side effects. [ABSTRACT FROM AUTHOR]

Enhanced quality and reduced on-site construction time are the basic features of prefabricated bridge elements and systems. Prefabricated lightweight bridge decks have already started finding their place in accelerated bridge construction (ABC). Therefore, the development of deck panels using high strength and high performance concrete has become an active area of research. Further optimization in such deck systems is possible using prestressing or replacement of raw materials with sustainable and recyclable materials. This research involves experimental evaluation of six full-depth precast prestressed high strength fiber-reinforced concrete (HSFRC) and six partial-depth sustainable ultra-high performance concrete (sUHPC) composite bridge deck panels. The composite panels comprise UHPC prepared with ground granulated blast furnace slag (GGBS) with the replacement of 30% cement content overlaid by recycled aggregate concrete made with replacement of 30% of coarse aggregates with recycled aggregates. The experimental variables for six HSFRC panels were depth, level of prestressing, and shear reinforcement. The six sUHPC panels were prepared with different shear and flexural reinforcements and sUHPC-normal/recycled aggregate concrete interface. Experimental results exhibit the promise of both systems to serve as an alternative to conventional bridge deck systems. [ABSTRACT FROM AUTHOR]

The two cationic palladium(II) complexes, [Pd(Len)2][OTf]2 (4) and [Pd(Lphen)2][OTf]2 (5), were synthesized by treatment of bis(benzonitrile)dichloropalladium(II) with [H2Len][OTf]2 (2) or [H2Lphen][OTf]2 (3), respectively, in the presence of a weak base. The pro-ligands 2 and 3 were synthesized by melt reactions between N-methyl-4-chloropyridinium triflate (1) and the amines ethylenediamine or phenylenediamine, respectively. The water-soluble compounds 2–5 were fully characterized, including by single-crystal X-ray crystal structure determinations for 2–4. UV-Vis and fluorescence spectroscopy were used to study the binding interactions of 2–5 with CT-DNA. The spectroscopic data suggested the presence of intercalative and groove binding modes and this was supported by molecular docking studies. The in vitro cytotoxicity studies (IC50 values) showed that the human breast cancer cell lines MCF-7 and T47D were more sensitive towards 3, 4 and 5 than cisplatin. The cytotoxicity of the new compounds decreased in the order 5 > 4 > 3 > 2. Furthermore, the annexin V-FITC staining method strongly suggested the presence of phosphatidylserine (PS) on the outer membrane of the treated cells, which is a hallmark of apoptosis. [ABSTRACT FROM AUTHOR]

Cyclohexenone containing chalcones core is one important class of materials, which exhibit high nonlinear optical (NLO) responses and good crystallizability. The present study reports the successful development of six new fluorescent cyclohexenone derivatives (CDs) via conventional method. The molecular structures of these newly synthesized CDs were confirmed by using various such as 1H NMR, 13C NMR, FTIR, EIMS, UV-Vis spectroscopy and single crystal X-ray diffraction. The crystallographic data revealed that the spatial structure of the representative CD (4BE) belongs to monoclinic, P21/c space group. The results from luminescence studies show that the CDs molecules apparently emit intense green light at room temperature in aqueous media. The relative polarity and molecular of the CDs molecules were predicted by measuring the molecular electrostatic potential and frontier molecular orbital energy. In addition, the UV-Vis spectra, transition character and electronic structures of these CDs were computed by using quantum chemical methodology. It was interesting to note that the values of computed and experimental electronic transitions (λmax) were in good agreement and these CDs display high hyperpolarizability ( β) values. The present work will be helpful for systematical understanding of the structures and the optical properties of CDs for studying the that will suggest their potential application in . Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

New water-soluble pyridinium amines ( 2-8) were obtained by the solid-state reactions of 4-chloro-1-methylpyridin-1-ium triflate ( 1) and various primary aromatic amines. These compounds were characterized by 1H, 13C NMR, FTIR, UV-vis, and fluorescence spectroscopic methods along with single-crystal X-ray structure determination. The interaction potentials of all newly synthesized compounds with calf thymus DNA ( CT-DNA) were investigated by UV-vis and florescence spectroscopy accompanied by docking studies. UV-vis spectroscopy indicated that the binding of compounds with CT-DNA takes place via the intercalative mode. The compounds were also screened for their potential as antioxidants and enzyme inhibition agents. Some compounds displayed excellent butyrylcholine and acetylcholine esterase inhibition activities and were effective in scavenging the 2,2-diphenyl-1-picrylhydrazyl ( DPPH) radical in a dose-dependent manner comparable to a standard. [ABSTRACT FROM AUTHOR]

• A series of novel mononuclear and dinuclear Silver(I)-NHC complexes are synthesized and characterized. • Very low catalyst loading (0.1 mol%) is required for the carbon dioxide insertion into epoxides. • No solvent and co-catalyst are required using the Ag-compounds. • Catalysts are highly robust demonstrating excellent conversions selectivity > 99 %. • The novel catalyst is highly active amongst the reported silver catalysts for CO 2 /epoxides couplings. A series of left-to-right inequivalent 1,3-disubstituted benzimidazolium halide pro-ligands having the general formula [RBNHCCH2OxMe][X] (R = 3-Me-Bn, 3,5-Me 2 -Bn, 2,4,6-Me 3 -Bn, 2,3,5,6-Me 4 -Bn, 2,3,4,5,6-Me 5 -Bn, 3,4,5-(OMe) 3 -Bn, or 4-tBu-Bn; X = Cl, Br) were synthesized by the alkylation of 1-((3-methyloxetan-3-yl)methyl)benzimidazole. The corresponding Ag complexes, (RBNHCCH2OxMe)AgX, were prepared following pro-ligand addition to Ag 2 O. These compounds were characterized using spectroscopic techniques such as FT-IR, NMR spectroscopy, and single-crystal X-ray diffraction. The solid-state structure of (3-Me-BnBNHCCH2OxMe)AgCl revealed a linear monomer while [(2,4,6-Me3-BnBNHCCH2OxMe)AgCl] 2 was found to exist as a dimer with pseudo trigonal planar geometry about each metal center. The synthesized (RBNHCCH2OxMe)AgX complexes were found to be efficient for the addition of carbon dioxide to epoxides to yield value-added cyclic carbonates at ambient pressure. Amongst the investigated complexes, the bimetallic complex [(2,4,6-Me3-BnBNHCCH2OxMe)AgCl] 2 was found to be the most active for CO 2 insertion, exhibiting favorable activity when compared to known NHC complexes. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Design and synthesis of 2-phenylchromones as the potent tyrosinase inhibitors. • Compound 10 showed the excellent inhibitory activity (IC 50 = 0.093 ± 0.003 µg/ml). • Molecular docking studies of these compounds were performed. • Structure-activity relationship (SAR) was established. • ADME screening (in silico) of the synthesized analogues displayed drug-like nature. The present study describes the discovery of novel inhibitors of mushroom tyrosinase enzyme. For that purpose, a series of varyingly substituted 2-phenylchromone analogues 1–28 were synthesized and characterized in detail by various spectroscopic techniques (UV–Vis, FTIR, 1H NMR, 13C NMR) and mass spectrometry. All the derivatives (1–28) were screened in vitro for their inhibitory potential against mushroom tyrosinase enzyme. Interestingly, all the synthetic compounds displayed good to excellent inhibitory activity with IC 50 values ranging from 0.093 ± 0.003 μg/ml to 23.58 ± 0.94 μg/ml for brominated 3-hydroxy-2-phenylchromones and 0.22 ± 0.017 μg/ml to 22.22 ± 1.1 μg/ml for brominated 2-phenylchromones against tyrosinase in comparison to the standard kojic acid (IC 50 = 1.79 ± 0.64 μg/ml). Remarkably, the bromine atoms attached on ring A attribute to increases the inhibitory potential of 2-phenylchromone moiety and anti-tyrosinase assay demonstrated that compound 10 (IC 50 = 0.093 ± 0.003 µg/ml) was found almost nineteenfold , 11 (IC 50 = 0.126 ± 0.015 µg/ml) fourteenfold and 26 (IC 50 = 0.22 ± 0.017 µg/ml) about eightfold more active than the positive control. Notably, among the already literature reported tyrosinase inhibitors, these analogues have been found the most active inhibitors of mushroom tyrosinase with the lowest possible IC 50 values. To design and develop novel tyrosinase inhibitors using 2-phenylchromone as a structural motif in the future, a limited structure-activity relationship was established. Moreover, in silico studies were carried out to rationalize the binding mode of interactions of all the targeted compounds (1–28) with the active site of enzymes. The experimental and theoretical results are in parallel with one another. In addition, molecular description was performed with the drug-likeness and bioactivity scores. Computational analysis predicted that few compounds are in a linear correlation with Lipinski's RO5 indicating superb drug-likeness and bioactivity score for drug targets. [ABSTRACT FROM AUTHOR]

The three dimensional anionic Mn(II)-Oxalate coordination polymer has excellent water oxidation catalytic activity that may offer some new guidance for the design and preparation of highly efficient oxalate based 3D coordination polymers of first row transition metals for WOC. A novel three dimensional coordination polymer {[Mn(ox) 3/2 ][bap].(H 2 O)} n , (1) (ox = oxalate, bap = N -benzyl-4-aminopyridinium) is reported in this work as an efficient electrocatalyst for oxygen evolution reaction (OER). 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) based dispersion condition as well as interactions between the adjacent layers of anionic coordination polymer and N -benzyl-4-aminopyridinium were found necessary for the growth and stability of this architecture. Single crystal XRD, IR and elemental analysis confirmed the formation of compound (1). Morphology and thermal stability were evaluated by SEM and TG respectively. Electrochemical studies were carried out in a three-electrode system using 1 coated FTO as a working electrode using 0.1 M KOH solution. The electrochemical investigation showed that 1 produced a current density of 10 mAcm−2 at a relatively low overpotential (η = 404 mV) while a maximum current density of 62 mAcm−2 was achieved. A catalytic onset potential for OER was observed at 1.5 V (vs RHE) and needed overpotential of 258 mV. The catalyst offered a turnover frequency (TOF) of 0.06 s−1 for OER at 404 mV. Long-term stability measurements of 1 were recorded by using chronoamperometry, IR analysis and LS voltammograms for the pristine and post-catalytic 1 coated FTO electrodes that confirmed the durability of the catalyst. The fascinating electrochemical behaviour of 1 toward oxygen evolution reaction can be attributed to its 3D polymeric structure and represents 1 as a robust and efficient catalyst towards OER. [ABSTRACT FROM AUTHOR]

• A series of new flavonols and 4-thioflavonols were designed, synthesized and characterized efficiently. • The inhibitory potentials of all the synthesized compounds were evaluated against cholinesterase enzymes. • Structure-activity relationship was established. • In silico molecular modeling studies were performed. To explore new scaffolds for the treat of Alzheimer's disease appears to be an inspiring goal. In this context, a series of varyingly substituted flavonols and 4-thioflavonols have been designed and synthesized efficiently. All the newly synthesized compounds were characterized unambiguously by common spectroscopic techniques (IR, 1H-, 13C NMR) and mass spectrometry (EI-MS). All the derivatives (1 – 24) were evaluated in vitro for their inhibitory potential against cholinesterase enzymes. The results exhibited that these derivatives were potent selective inhibitors of acetylcholinesterase (AChE), except the compound 11 which was selective inhibitor of butyrylcholinesterase (BChE), with varying degree of IC 50 values. Remarkably, the compounds 20 and 23 have been found the most potent almost dual inhibitors of AChE and BChE amongst the series with IC 50 values even less than the standard drug. The experimental results in silico were further validated by molecular docking studies in order to find their binding modes with the active pockets of AChE and BChE enzymes. [ABSTRACT FROM AUTHOR]

• New analogs of N -(3-trifluoromethyl)benzoyl- N′ -aryl thiourea are reported. • All synthesized compounds were screened for their antibacterial, antifungal, antioxidant and cytotoxic activities with some significant results. • These compounds were also evaluated for their antiurease potential with promising results. • All the synthesized compounds were docked into the binding cavity of Urease and showed valuable interactions with the target protein along with good docking scores. • Thus we propose the synthesized compounds to be used as potent urease inhibitors after further detailed mechanistic studies. An irrefutable advancement has been noted for the infectious diseases caused due to ureolytic bacteria through the development of various drugs. Keeping in mind the extremely valuable synthetic utility and medicinal significance of thiourea derivatives, synthesis of new 3-trifluoromethyl benzoic acid thiourea derivatives (3a–j) were carried out. The biological potential of all compounds in terms of antimicrobial, antioxidant, cytotoxic and antiurease activities were studied. The compounds 3a, 3c and 3i with dichloro and methoxy groups substitution on the aryl group showed significant activity against all strain of bacteria while moderate to no activity was observed in remaining compounds. Whereas the antifungal evaluation showed that all compounds were active againts C. Albican and no activity was observed against C. Prapsilosis. The cytotoxic findings revealed the non-toxic nature of these compounds as IC 50 values of majority of the compounds are above 100 μm except for compounds 3f and 3g. In addition, these compounds exhibited better antioxidant potential as 100 μm concentration inhibited >50% reactive oxygen species (ROS) production except compounds 3e, 3f and 3j. The compound 3a proved to be the most potent urease inhibitor showing the highest enzyme % inhibition (93.1%) with IC 50 value of 8.17 ± 0.24 µM and found more active as compare to standard followed by compound 3e (92.6%), 3h (91.6%), 3d (90.8%), 3b (90.6%) and 3f (90.0%) with their respective IC 50 values. All the synthesized compounds were docked into the binding cavity of Urease (PDB ID: 4ubp). The most active compound 3a was also ranked as top on the docking score as it was found to show valuable interactions with the target protein along with good docking scores. Hence our results revealed that the synthesized compounds have potential to be used as potent urease inhibitors after further detailed mechanistic studies. [ABSTRACT FROM AUTHOR]

Background:  Total knee arthroplasty (TKA) may result in significant blood loss, but it is an effective and affordable treatment for severe osteoarthritis in the knees. While intravenous (IV) tranexamic acid (TXA) is a commonly used technique, intraarticular (IA) TXA has just recently started to gain traction in joint replacement procedures. The purpose of this research was to examine the mean postoperative hemoglobin concentration in order to assess the effectiveness of TXA administered IV vs IA after TKA., Objective: To assess the effectiveness of intraarticular TXA against intravenous administration., Materials and Methods: The six-month randomized controlled experiment was started from October 5, 2022, to April 4, 2023, at "the Orthopedics Department of Sir Ganga Ram Hospital in Lahore". The experiment included 60 patients undergoing TKA, ranging in age from 30 to 70. All members of the surgical team, including the supervisor (a consultant surgeon), assistants, and researchers, were present throughout the surgery. A high, thigh tourniquet was employed in every case, and a medial parapatellar technique was performed as well. Before the tourniquet was inflated, individuals in the intravenous group received 1 g of TXA intravenously 15-30 minutes beforehand. In the IA group, the "patient received an injection of 2 g of TXA in a 20 mL solution" straight into the joint after the prosthesis was implanted and secured. Data were analyzed using SPSS (version 26), with numerical data (age, BMI, surgical length, and hemoglobin levels) presented as mean ± SD and categorical factors (gender, American Society of Anesthesiologists (ASA) class, anatomical side) shown as frequency and percentage. The mean postoperative hemoglobin levels were compared between groups using an independent sample t-test, with data stratified by various factors and p ≤ 0.05 considered significant., Results: There were 60 patients in this study, ranging in age from 30 to 70. The mean±SD age was 48.73±10.35 years. Patients' mean BMI was 25.51±4.48 kg/m², with representation across underweight, normal, overweight, and obese categories. The procedure took 173.10±32.61 minutes. The overall postoperative hemoglobin concentration was significantly higher in the IA TXA group (12.12±1.32 g/dL) compared to the IV TXA group (11.11±1.10 g/dL), with a p-value of 0.02. Additionally, when stratified by age, the IA TXA group consistently demonstrated higher postoperative hemoglobin levels across all age brackets, with significant differences observed in the 51-60 years (p = 0.001) and 61-70 years (p = 0.011) groups. Gender-based comparisons showed that IA TXA was associated with higher postoperative hemoglobin levels for both males (p < 0.05) and females (p < 0.05) compared to IV TXA., Conclusion: This study demonstrates that IA administration of TXA is more effective in maintaining higher postoperative hemoglobin concentrations compared to IV TXA in patients undergoing TKA. The IA TXA group consistently achieved significantly higher hemoglobin levels across various age groups and both genders, indicating superior efficacy in reducing blood loss associated with TKA. These findings suggest that IA TXA could be a preferable alternative to IV TXA for enhancing postoperative hemoglobin recovery and potentially improving patient outcomes in knee arthroplasty procedures., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Review Committee of the College of Physicians and Surgeons Pakistan (CPSP) issued approval CPSP/REU/OSG-2021-059-2658. The ethical review committee of the College of Physicians and Surgeons Pakistan (CPSP) approved the study, which was carried out in compliance with ethical guidelines, under reference number CPSP/REU/OSG-2021-059-2658, dated September 15, 2022. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Aslam et al.)

The excelling role of organic chemistry in the medicinal field continues to be one of the main leads in the drug development process. Particularly, this industry requires organic chemists to discover small molecular structures with powerful pharmacological potential. Herein, a diverse range of chalcone (1-11) and aurone (12-22) derivatives was designed and synthesized and for the first time, and both motifs were evaluated as potent inhibitors of alkaline phosphatases (APs). Structural identification of the target compounds (1-22) was accomplished using common spectroscopic techniques. The effect of the nature and position of the substituent was interestingly observed and justified based on the detailed structure-activity relationship (SAR) of the target compounds against AP. It was concluded from the obtained results that all the newly synthesized compounds exhibit high inhibitory potential against the AP enzyme. Among them, compounds 12 (IC 50 = 2.163 ± 0.048 μM), 15 (IC 50 = 2.146 ± 0.056 μM), 16 (IC 50 = 2.132 ± 0.034 μM), 18 (IC 50 = 1.154 ± 0.043 μM), 20 (IC 50 = 1.055 ± 0.029 μM) and 21 (IC 50 = 2.326 ± 0.059 μM) exhibited excellent inhibitory activity against AP, and even better/more active than KH 2 PO 4 (standard) (IC 50 = 2.80 ± 0.065 μM). Remarkably, compound 20 (IC 50 = 1.055 ± 0.029 μM) may serve as a lead structure to design more potent inhibitors of alkaline phosphatase. To the best of our knowledge, these synthetic compounds are the most potent AP inhibitors with minimum IC 50 values reported to date. Furthermore, a molecular modeling study was performed against the AP enzyme (1EW2) to check the binding interaction of the synthesized compounds 1-22 against the target protein. The Lineweaver-Burk plots demonstrated that most potential derivative 20 inhibited h-IAP via a non-competitive pathway. Finally, molecular dynamic (MD) simulations were performed to evaluate the dynamic behavior, stability of the protein-ligand complex, and binding affinity of the compounds, resulting in the identification of compound 20 as a potential inhibitor of AP. Accordingly, excellent correlation was observed between the experimental and theoretical results. The pharmacological studies revealed that the synthesized analogs 1-22 obey Lipinski's rule. The assessment of the ADMET parameters showed that these compounds possess considerable lead-like characteristics with low toxicity and can serve as templates in drug design., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Cancer is an uncontrolled multiplication of cells. The desire efficacy and severe toxicity of current anticancer drugs urge exploring and investigating a better alternative to existing chemotherapeutics. Natural products of marine origin are excellent sources of potential new drugs of enhanced biological activities., Objectives: Thus, the cytotoxic effects along with investigating the mode of cell death exerted by fractions, AP-9, AP-THR, DS-8 and DS-9 fraction of Acanthaster planci, Diadema setosum sp., on the human cervical cancer cell line, HeLa., Methods: The cytotoxicity of fractions has determined by using an MTS assay. The early and late apoptosis was studied by using the High content Screening (HCS) instrument., Results: The four fractions produced effective cytotoxicity effects with IC50 values at 72hr of less than 20 μg/ml in the order of AP-9 > DS-9 > APTHR-9 > DS-8. The fraction s exhibited cytotoxicity via mediating apoptotic mode of cell death. The early apoptosis by exposure of phosphatidylserine to the outer leaflet of the plasma membrane and late apoptosis due to the presence of green stain (DNA fragmentation) in treated cells., Conclusion: The potent bioactive compounds might be responsible for inducing apoptosis in cancer cells and, thus, the potential to be a successful candidate for exploring upcoming chemotherapeutic drugs.

Objective: Liver cancer is one of the most common causes of cancer death, with reduced survival rates. The development of new chemotherapeutic agents is essential to find effective cytotoxic drugs that give minimum side effects to the surrounding healthy tissues. The main objective of the present study was to evaluate the cytotoxic effects and mechanism of cell death induced by the crude and diethyl ether extract of Xylocarpus mouccensis on the human hepatocellular carcinoma cell line., Methods: The cytotoxicity activity was measured using the MTS assay. The mode of cell death determined by the apoptosis study, DNA fragmentation analysis done by using the TUNEL system. The pathway study or mechanism of apoptosis observed by study caspases 8, 9, 3/7 Glo-caspases method., Results: In this study, the methanol extracts prepared from leaf Xylocarpus mouccensis leaf produced cytotoxicity effect with IC50 (72hr) < 30µg/ml. The IC50 value at 72 hours exerted by diethyl ether extract of Xylocarpus moluccensis leaf was 0.22 µg/ml, which was more cytotoxic than to that of crude methanol extract. The results obtained by the colorimetric TUNEL system suggest that methanol crude extract of Xylocarpus moluccensis (leaf), diethyl ether extract of Xylocarpus moluccensis (leaf) and methanol extract of Xylocarpus granatum (bark) induced DNA fragmentation in the HepG2 cell line. Besides, the caspase-Glo assay demonstrated that diethyl ether leaf extract of Xylocarpus moluccensis triggered apoptotic cell death via activation of caspases -8, and -3/7 However, no visible activation was noticed for caspase -9. Furthermore, TLC indicates the presence of potential metabolites in an extract of Xylocarpus moluccensis., Conclusion: Thus, the present study suggests the remarkable potential of active metabolites in the extract of Xylocarpus moluccensis as a future therapeutic agent for the treatment of cancer., .

A series of different substituted terpyridine (tpy)-based ligands have been synthesized by Kröhnke method. Their binding behaviour was evaluated by complexing them with Co(II), Fe(II) and Zn(II) ions, which resulted in interesting coordination compounds with formulae, [Zn(tpy) 2 ]PF 6 , [Co(tpy) 2 ](PF 6 ) 2 , [Fe(tpy) 2 ](PF 6 ) 2 and interesting spectroscopic properties. Their absorption and emission behaviours in dilute solutions were investigated in order to explain structure-property associations and demonstrate the impact of different aryl substituents on the terpyridine scaffold as well as the role of the metal on the complexes. Photo-luminescence analysis of the complexes in acetonitrile solution revealed a transition from hypsochromic to bathochromic shift. All the compounds displayed remarkable photo-luminescent properties and various maximum emission peaks owing to the different nature of the functional groups. Furthermore, the anti-microbial potential of ligands and complexes was evaluated with docking analyses carried out to investigate the binding affinity of terpyridine-based ligands along with corresponding proteins (shikimate dehydrogenase and penicillin-binding protein) binding sites. To obtain further insight into molecular orbital distributions and spectroscopic properties, density functional theory calculations were performed for representative complexes. The photophysical activity and interactions between chromophore structure and properties were both investigated experimentally as well as theoretically., Competing Interests: There are no conflicts of interest to declare., (© 2020 The Authors.)

Breast cancer is among the frequently occurring cancer worldwide. The foremost underline aim of this study was to determine the growth inhibitory effect along with mechanistic study of a Bruguiera gymnorrhiza extract on MCF-7. The cytotoxicity activity was determined by using the MTS assay. Butanol extract exhibited the maximum cytotoxicity activity against the MCF-7 cells with IC 50 of 3.39 μg/mL, followed by diethyl ether and methanol extract (IC 50 at 16.22 μg/mL and 37.15 μg/mL, respectively) at 72 h. The DeadEnd TM Colorimetric Apoptosis Detection System confirmed the induction of apoptosis (via DNA fragmentation) in MCF-7 cells. Both butanol and diethyl ether extracts of B. gymnorrhiza significantly increase the caspase-3 level. However, the diethyl ether extract induced higher caspase-9 levels compared to caspase-8, suggesting that the intrinsic pathway was the major route in the process of apoptosis. Thin-layer chromatography profiling demonstrated the presence of phenolic, terpene, and alkaloid compounds in crude methanol, diethyl ether, and butanol extracts. The phytochemicals present in the extracts of B. gymnorrhiza might have the potential to be a future therapeutic agent against breast cancer., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Advanced Pharmaceutical Technology & Research.)

Cancer is a complex multifactorial disease and leading causes of death worldwide. Despite the development of many anticancer drugs, there is a reduced survival rate due to severe side effects. The nontargeted approach of convention drugs is one of the leading players in context to toxicity. Hyaluronan is a versatile bio-polymer and ligand of the receptor (CD44) on cancer cells. The MCF-7 and HT-29 cancer cell lines treated with hyaluronic acid-paclitaxel (HA-PTX) showed the distinguishing morphological features of apoptosis. Flow cytometric analysis showed that HA-PTX induces apoptosis as a significant mode of cell death. The activation level of tumor suppressor protein (p53) increased after PTX treatment in MCF-7, but no changes observed in HT-29 might be due to hereditary mutations. The lack of suppression in AKT and Rho A protein suggest the use of possible inhibitors in future studies which might could play a role in increasing the sensitivity of drug towards mutated cells line and reducing the possibilities for cancer cell survival, migration, and metastasis., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Advanced Pharmaceutical Technology & Research.)