Electrochemical immunosensing of tumor markers.

The rising incidence and mortality rates of cancer have led to a growing need for precise and prompt early diagnostic approaches to effectively combat this disease. However, traditional methods employed for detecting tumor cells, such as histopathological and immunological techniques, are often associated with complex procedures, high analytical expenses, elevated false positive rates, and a dependence on experienced personnel. Tracking tumor markers is recognized as one of the most effective approaches for early detection and prognosis of cancer. While onco-biomarkers can also be produced in normal circumstances, their concentration is significantly elevated when tumors are present. By monitoring the levels of these markers, healthcare professionals can obtain valuable insights into the presence, progression, and response to treatment of cancer, aiding in timely diagnosis and effective management. This review aims to provide researchers with a comprehensive overview of the recent advancements in tumor markers using electrochemical immunosensors. By highlighting the latest developments in this field, researchers can gain a general understanding of the progress made in the utilization of electrochemical immunosensors for detecting tumor markers. Furthermore, this review also discusses the current limitations associated with electrochemical immunosensors and offers insights into paving the way for further improvements and advancements in this area of research.

One pot fabrication of diamino naphthalene -AuNPs decorated graphene nanoplatform for the MRSA detection in the biological sample.

Early monitoring of MRSA can effectively mitigate the disease risk by using Penicillin-binding protein 2a (PbP2a) biomarker. Diamino naphthalene-AuNPs decorated graphene (AuNPsGO-DN) nanocomposite was synthesized for a rapid and sensitive immunosensor detecting PbP2a. The synthesized AuNPsGO-DN nanocomposites were characterized by field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (SEM-EDX), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, and X-ray diffraction spectroscopy (XRD). Electrochemical characterization done with cyclic voltammetry (CV), differential pulse voltammetry (DPV), and electrical impedance spectroscopy (EIS) techniques. Anti-PbP2a monoclonal antibodies immobilized at AuNPsGO-DN/GCE via covalent bonding. AuNPs enhanced the electrode surface area and the antibodies' loading. Mercaptopropionic acid (MPA) was a linker between the AuNPs and antibodies, orientated the antibodies as opposite to the PbP2a antigen, and improved the sensitivity and specificity. The antiPbP2a/MPA/AuNPsGO-DN/GCE electrode displayed sensitive and selective detection towards the PbP2a antigen in phosphate buffer saline (PBS pH 7.4). The broad linear range from 0.01 to 8000 pg/mL was obtained with LOD of 0.154 pg/mL and 0.0239 pg/mL, respectively. A label-free, simple, and sensitive immunosensor was developed with a 98-106 % recovery rate in spiked biological samples. It shows the potential applicability of the developed immunoelectrode.

Palladium-Catalyzed C-H Olefination of Imidazo[1,2a] pyridine Carboxamide in Aqueous Ethanol under Oxygen.

The advancement of sustainable chemistry and changes in the economy are strongly intertwined. Reaction time, cost savings, moderate temperatures, and generation of the fewest byproducts are frequently achieved by using catalytic processes. Herein, we report the C-H olefination of imidazo[1,2a] pyridine carboxamides with various acrylates in the presence of Pd (OAc)2 with O2 as the oxidant in aqueous ethanol rather than using non-ecofriendly solvents. The C-H activation features most user-friendly reaction conditions, excellent yield as well as plenty substrate scope and applicable for C-H deuteriation of the corresponding heteroarenes with D2O. Experimental mechanistic studies indicate that C-H activation step succeeded after formation of tetra coordinated square planer Pd-substrate adduct.

Rapid and label-free A2 peptide epitope decorated CoFe2O4-C60 nanocomposite-based electrochemical immunosensor for detecting Visceral Leishmaniasis.

Diagnosis of Visceral Leishmaniasis is challenging due to the shared clinical features with malaria, typhoid, and tuberculosis. A CoFe2O4-C60 nanocomposite-based immunosensor decorated with a sensitive A2 peptide antigen was fabricated to detect anti-A2 antibodies for application in visceral leishmaniasis diagnosis. The flame-synthesised nanocomposite was characterised using Fourier Transform Infrared spectroscopy (FTIR), X-ray diffraction spectroscopy (XRD), Scanning electron microscopy (SEM), Energy dispersive X-ray spectroscopy (EDX), Raman spectroscopy and electrochemical impedance spectroscopy (EIS) techniques. N terminated specific A2 peptide epitope antigen (NH2-QSVGPLSVGP-OH) was synthesised and characterised by high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectroscopy (LC-MS). Using EDC/NHS, A2 peptide antigen (Apg) was immobilised on the CoFe2O4-C60-modified electrode. The performance of the immunosensor, Apg-CoFe2O4-C60NP/GCE, was evaluated by testing its ability to detect varying concentrations of anti-A2 antibody solution in PBS and spiked serum with 1 mM [Fe(CN)6]3-/4- in 0.01 M PBS (pH 7.4) as supporting electrolyte. using differential pulse voltammetry. The immunosensor showed excellent reproducibility and a linear range of 10-10-10-1 µg/mL, with an experimental detection limit of 30.34 fg/mL. These results suggest that the fabricated sensor has great potential as a tool for diagnosing visceral leishmaniasis.

Palladium-Catalyzed Regiodivergent C-H Olefination of Imidazo[1,2a]pyridine Carboxamide and Unactivated Alkenes.

Despite remarkable successes in linear and branched vinyl (hetero) arene synthesis, regiodivergent C-H olefination with a single catalytic system has remained underdeveloped. Overcoming this limitation, a Pd/MPAA-catalyzed regiodivergent C-H olefination of imidazo[1,2a] pyridine carboxamides with unactivated terminal alkenes to generate branched and linear olefinated products depending upon the electronic nature of alkenes is reported herein. Moreover, this protocol can be applied for C-H deuteriation of the corresponding heteroarenes with D2 O as deuterium source. Preliminary experimental studies combined with computational investigations (DFT studies) suggest that regiodivergent olefination can be controlled by olefin insertion and ß-hydride elimination steps.

Recent advancement of HDAC inhibitors against breast cancer.

Recent studies highlight the great potential impact of HDAC inhibitors (HDACis) in suppressing TNBC, even though clinical trials including a single HDACis demonstrated unsatisfactory outcomes against TNBC. New compounds created to achieve isoform selectivity and/or a polypharmacological HDAC strategy have also produced interesting results. The current study discusses the HDACis pharmacophoric models and the structural alterations that produced drugs with strong inhibitory effects on TNBC progression. With more than 2 million new cases reported in 2018, breast cancer-the most common cancer among women worldwide-poses a significant financial burden on an already deteriorating public health system. Due to a lack of therapies being developed for triple-negative breast cancers and the development of resistance to the current treatment options, it is imperative to plan novel therapeutics in order to bring new medications to the pipeline. Additionally, HDACs deacetylate a large number of nonhistone cellular substrates that control a variety of biological processes, such as the beginning and development of cancer. The significance of HDACs in cancer and the therapeutic potential of HDAC inhibitor. Furthermore, we also reported molecular docking study with four HDAC inhibitors and performed molecular dynamic stimulation of the best dock score compound. Among the four ligands belinostat compound showed best binding affinity with histone deacetylase protein which was -8.7 kJ/mol. It also formed five conventional hydrogen bond with Gly 841, His 669, His 670, pro 809, and His 709 amino acid residues.

Isoflavonoid and Furanochromone Natural Products as Potential DNA Gyrase Inhibitors: Computational, Spectral, and Antimycobacterial Studies.

In pursuit of new antitubercular agents, we here report the antimycobacterial (H37Rv) and DNA gyrase inhibitory potential of daidzein and khellin natural products (NPs). We procured a total of 16 NPs based on their pharmacophoric similarities with known antimycobacterial compounds. The H37Rv strain of M. tuberculosis was found to be susceptible to only two out of the 16 NPs procured; specifically, daidzein and khellin each exhibited an MIC of 25 µg/mL. Moreover, daidzein and khellin inhibited the DNA gyrase enzyme with IC50 values of 0.042 and 0.822 µg/mL, respectively, compared to ciprofloxacin with an IC50 value of 0.018 µg/mL. Daidzein and khellin were found to have lower toxicity toward the vero cell line, with IC50 values of 160.81 and 300.23 µg/mL, respectively. Further, molecular docking study and MD simulation of daidzein indicated that it remained stable inside the cavity of DNA GyrB domain for 100 ns.

A concise review on marine bromopyrrole alkaloids as anticancer agents.

Natural products have been the most important sources of chemically diverse raw materials that have inspired pharmaceutical discoveries over the past few decades. Many pharmaceutical companies are utilizing plant extracts to develop relatively crude therapeutic formulations. The interesting chemicals identified as natural products are derived from the phenomenon of biodiversity, where the interactions between the organisms and their environment formulate the diverse and complex chemical entities within them that enhance their survival and competitiveness. Marine sponges are rich sources of natural products and have provided an infinite supply of bioactive metabolites. Bromopyrrole alkaloids are a good example of marine metabolites, have a broad range of biological activity, and represent a fascinating example of chemical diversity of secondary metabolites elaborated by marine invertebrates. The isolation and synthesis of this structural class have been investigated, resulting in a series of bromopyrrole alkaloids with potential lead hits. This review presents the detailed isolation and anticancer activity of marine bromopyrrole alkaloids, and will be of interest to the wider research community both in academic and industrial settings.

Recent Literature Review on Coumarin Hybrids as Potential Anticancer Agents.

Cancer is considered one of the leading causes of death globally, especially patients with lung, pancreatic, or brain tumors are most likely to die of cancer, and patients with prostate and breast cancer are at a high risk of noncancer death. As a result, there is ongoing research regarding developing new, safe, and efficient anticancer agents. Coumarin-based naturally occurring compounds possess a broad spectrum of activity in medicinal chemistry, such as anticancer, anti-inflammatory, antimicrobial, antioxidant agents, etc. Many researchers have synthesized coumarinbased novel therapeutic agents via molecular hybridization technique, which offers an excellent opportunity to develop novel compounds with improved biological activities by incorporating two or more pharmacophores. This review aims to shed light on the recent developments of coumarin-based anticancer hybrid derivatives and their Structure-Activity Relationships (SAR). This review serves as a medium that medicinal chemists could utilize to design and synthesize coumarin derivatives with significant pharmacological value as future anticancer agents.

O-Benzoylhydroxylamines: A Versatile Electrophilic Aminating Reagent for Transition Metal-Catalyzed C-N Bond-Forming Reactions.

Owing to the prevalence of nitrogen-containing compounds in natural products and important pharmaceutical agents, chemists, have actively searched for the development of efficient and selective methodologies allowing for the facile construction of carbon-nitrogen bonds. Over the last decade, transition metal-catalyzed C-N bond construction via electrophilic amination reaction has emerged as an attractive approach for the synthesis of various organic molecules and pharmaceuticals. Particularly, O-benzoylhydroxylamines as an electrophilic aminating agent have proven to be the best and most widely used in both academic and industrial research. In this review, we highlight the key contributions to the recent transition metal-catalyzed C-N bond formation reactions using O-benzoylhydroxylamines as an aminating agent and their relevant mechanistic insights.

An Overview on Synthetic and Medicinal Perspectives of [1,2,4]Triazolo[1,5-a]pyrimidine Scaffold.

[1,2,4]Triazolo[1,5-a]pyrimidine is an important heterocyclic scaffold known to have a wide range of pharmacological activities such as anticancer, antimicrobial, anti-tubercular, CB2 cannabinoid agonists, feticide, and adenosine antagonists. Several clinical trials and marketed drugs such as Trapidil, Essramycin, Pyroxsulam, DSM-265, Flumetsulam, GNF-6702, and Cevipabulin indicate the potential of [1,2,4]triazolo[1,5-a]pyrimidine moiety with various functional groups in medicinal chemistry. Herein, we represent a concise report focusing on the synthetic strategies used for diversely substituted [1,2,4]triazolo[1,5-a]pyrimidine analogs and their pharmacological applications. To the best of our knowledge, since 1980, we are the first to write a review on this emerging scaffold, which reveals the synthetic strategies, and pharmacological activities of differently substituted [1,2,4]triazolo[1,5-a]pyrimidine with special emphasis on structure-activity relationship studies.

Cu-catalysed transamidation of unactivated aliphatic amides.

Direct transamidation is gaining prominence as a ground-breaking technique that generates a wide variety of amides without the requirement of acid-amine coupling or other intermediate steps. However, transamidation of unactivated aliphatic amides, on the other hand, has been a long-standing issue in comparison to transamidation of activated amides. Herein, we report a transamidation approach of an unactivated aliphatic amide using a copper catalyst and chlorotrimethylsilane as an additive. In addition, we used transamidation as a tool for selective N-C(O) cleavage and O-C(O) formation to synthesise 2-substituted benzoxazoles and benzothiazoles. The reactions were carried out without using any solvents and offered wide substitution scope.

Repurposing antiviral phytochemicals from the leaf extracts of Spondias mombin (Linn) towards the identification of potential SARSCOV-2 inhibitors.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a pneumonia-like disease with a pattern of acute respiratory symptoms, currently remains a significant public health concern causing tremendous human suffering. Although several approved vaccines exist, vaccine hesitancy, limited vaccine availability, high rate of viral mutation, and the absence of approved drugs account for the persistence of SARS-CoV-2 infections. The investigation of possibly repurposing of phytochemical compounds as therapeutic alternatives has gained momentum due to their reported affordability and minimal toxicity. This study investigated anti-viral phytochemical compounds from ethanolic leaf extracts of Spondias mombin L as potential inhibitor candidates against SARS-CoV-2. We identified Geraniin and 2-O-Caffeoyl-(+)-allohydroxycitric acid as potential SARS-CoV-2 inhibitor candidates targeting the SARS-CoV-2 RNA-dependent polymerase receptor-binding domain (RBD) of SARS-CoV-2 viral S-protein and the 3C-like main protease (3CLpro). Geraniin exhibited binding free energy (ΔGbind) of - 25.87 kcal/mol and - 21.74 kcal/mol towards SARS-CoV-2 RNA-dependent polymerase and receptor-binding domain (RBD) of SARS-CoV-2 viral S-protein respectively, whereas 2-O-Caffeoyl-(+)-allohydroxycitric acid exhibited a ΔGbind of - 32 kcal/mol towards 3CLpro. Molecular Dynamics simulations indicated a possible interference to the functioning of SARS-CoV-2 targets by the two identified inhibitors. However, further in vitro and in vivo evaluation of these potential SARS-CoV-2 therapeutic inhibitor candidates is needed.

Lifestyles Shape the Cytochrome P450 Repertoire of the Bacterial Phylum Proteobacteria.

For the last six decades, cytochrome P450 monooxygenases (CYPs/P450s), heme thiolate proteins, have been under the spotlight due to their regio- and stereo-selective oxidation activities, which has led to the exploration of their applications in almost all known areas of biology. The availability of many genome sequences allows us to understand the evolution of P450s in different organisms, especially in the Bacteria domain. The phenomenon that "P450s play a key role in organisms' adaptation vis a vis lifestyle of organisms impacts P450 content in their genome" was proposed based on studies on a handful of individual bacterial groups. To have conclusive evidence, one must analyze P450s and their role in secondary metabolism in species with diverse lifestyles but that belong to the same category. We selected species of the phylum Proteobacteria classes, Alpha, Beta, Gamma, Delta, and Epsilon, to address this research gap due to their diverse lifestyle and ancient nature. The study identified that the lifestyle of alpha-, beta-, gamma-, delta-, and epsilon-proteobacterial species profoundly affected P450 profiles in their genomes. The study determined that irrespective of the species associated with different proteobacterial classes, pathogenic species or species adapted to a simple lifestyle lost or had few P450s in their genomes. On the contrary, species with saprophytic or complex lifestyles had many P450s and secondary metabolite biosynthetic gene clusters. The study findings prove that the phenomenon mentioned above is factual, and there is no link between the number and diversity of P450s and the age of the bacteria.

An Unprecedented Number of Cytochrome P450s Are Involved in Secondary Metabolism in Salinispora Species.

Cytochrome P450 monooxygenases (CYPs/P450s) are heme thiolate proteins present in species across the biological kingdoms. By virtue of their broad substrate promiscuity and regio- and stereo-selectivity, these enzymes enhance or attribute diversity to secondary metabolites. Actinomycetes species are well-known producers of secondary metabolites, especially Salinispora species. Despite the importance of P450s, a comprehensive comparative analysis of P450s and their role in secondary metabolism in Salinispora species is not reported. We therefore analyzed P450s in 126 strains from three different species Salinispora arenicola, S. pacifica, and S. tropica. The study revealed the presence of 2643 P450s that can be grouped into 45 families and 103 subfamilies. CYP107 and CYP125 families are conserved, and CYP105 and CYP107 families are bloomed (a P450 family with many members) across Salinispora species. Analysis of P450s that are part of secondary metabolite biosynthetic gene clusters (smBGCs) revealed Salinispora species have an unprecedented number of P450s (1236 P450s-47%) part of smBGCs compared to other bacterial species belonging to the genera Streptomyces (23%) and Mycobacterium (11%), phyla Cyanobacteria (8%) and Firmicutes (18%) and the classes Alphaproteobacteria (2%) and Gammaproteobacteria (18%). A peculiar characteristic of up to six P450s in smBGCs was observed in Salinispora species. Future characterization Salinispora species P450s and their smBGCs have the potential for discovering novel secondary metabolites.

DBU mediated one-pot synthesis of triazolo triazines via Dimroth type rearrangement.

Herein we report an efficient one-pot synthesis of [1,2,4]triazolo[1,5 a][1,3,5]triazines from commercially available substituted aryl/heteroaryl aldehydes and substituted 2-hydrazinyl-1,3,5-triazines via N-bromosuccinimide (NBS) mediated oxidative C-N bond formation. Isomerisation of [1,2,4]triazolo[4,3-a][1,3,5]triazines to [1,2,4]triazolo[1,5-a][1,3,5]triazines is driven by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) affording both isomers with good to excellent yields (70-96%).

Conglomeratin: a new antibacterial flavonol derivative from Macaranga conglomerata Brenan (Euphorbiaceae).

A new prenylated kaempferol, conglomeratin (1), alongside 7 known compounds including flavonoids (2 and 3), ellagic acid derivatives (4 and 5), triterpenoids (6 and 7), and a coumarin (8) were isolated from the leaves (1 - 5) and stem bark (6 - 8) of Macaranga conglomerata. Their structures were elucidated using spectroscopic and spectrometric techniques. The antibacterial assay was performed using disc diffusion method against Gram-positive and Gram-negative microorganisms. Compound 1 was significantly active against Pseudomonas aeruginosa ATCC 27853 (MIC = 7.8 µg/mL) and moderately active towards Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922 and Klebsiella pneumoniae ATCC 31488 (MIC = 62.5 µg/mL). Compound 2 showed potency against P. aeruginosa ATCC 27853 (MIC = 1.0 µg/mL) while 4 and 7 were selective towards K. pneumoniae ATCC 31488 (MIC = 7.8 and 1.0 µg/mL, respectively). These findings suggest that prenylation of flavonoids may contribute to improving their broad-spectrum antimicrobial activities.

Recent progress in electrochemical sensors for detection and quantification of malaria.

Malaria is still a major disease in sub-Saharan Africa and South-East Asia. This is despite different interventions by the World Health Organization (WHO), such as insecticide-treated mosquito net, antimalarial drugs, indoor residual spraying, and rapid diagnostic tools. In 2018, the mortality rate due to malaria was estimated to be 405 000, with children under five years accounting for 67% of all malaria deaths. Malaria can be prevented and treated using different strategies as recommended by WHO. However, the lack of rapid diagnostic tools with good selectivity and sensitivity is still a challenge. Therefore there is a need to develop rapid, low-cost, and portable analytical methods for quantifying malaria. This review focuses on the role of malaria biomarkers (Plasmodium falciparum Lactate Dehydrogenase (PfLDH), Plasmodium aldolase, Plasmodium falciparum Histidine-Rich Protein 2 (PfHRP2), Plasmodium falciparum Glutamate dehydrogenase (PfGDH), and Hemozoin) in diagnosis. Recent developments in nanomaterial-based electrochemical and colorimetric biosensors for malaria diagnosis are discussed. Finally, the review concludes with closing remarks and future perspectives of electrochemical biosensors.

Development of a DHA-Losartan hybrid as a potent inhibitor of multiple pathway-induced platelet aggregation.

Despite the scientific progression in the prevention and treatment of cardiovascular diseases (CVDs) they remain the leading cause of mortality and disability worldwide. The classic treatment involves the simultaneous dosing of two antiplatelet drugs, aspirin and clopidogrel/prasugrel. However, besides drug resistance, severe side effects have been also manifested including acute bleeding and toxicity. Thus, new therapeutic agents with enhanced efficacy and diminished side effects are of importance. Towards this end, omega-3 (ω-3) fatty acids have demonstrated potent efficacy against CVDs through inhibiting platelet aggregation that bears a pivotal role in atherothrombosis. Another factor that displays a critical role in the pathogenesis of cardiovascular diseases is the renin-angiotensin system (RAS), and especially the AT1R blocker losartan that has been reported to exert antiplatelet activity mediated by this receptor. Along these lines, we envisaged developing a molecular hybrid consisted of docosahexaenoic acid (ω-3 fatty acid) and losartan, that could exert a notable antiplatelet effect against CVDs. The design and synthesis of the new DHA-losartan hybrid, designated DHA-L, bestowed with the additive properties of the parent compounds, is reported. In silico studies were first exploited to validate the potential of DHA-L to retain losartan's ability to bind AT1R. The antiplatelet activity of DHA-L was evaluated against in vitro platelet aggregation induced by several platelet agonists. Notably, the hybrid illustrated a pleiotropic antiplatelet profile inhibiting platelet aggregation through multiple platelet activation pathways including P2Y12, PAR-1 (Protease-Activated Receptor-1), PAF (Platelet Activating Factor), COX-1 (cyclooxygenase-1) and collagen receptors. The stability of DHA-L in human plasma and in a wide range of pH values was also evaluated over time using an HPLC protocol. The hybridization approach described herein could pave the way for the development of novel potent multitargeted therapeutics with enhanced antiplatelet profile.Communicated by Ramaswamy H. Sarma.

Development of niosomes for encapsulating captopril-quercetin prodrug to combat hypertension.

Novel and effective anti-hypertensive agents are required to manage hypertension; therefore, we synthesised a novel antihypertensive drug from captopril and quercetin (cap-que) and explored its antihypertensive potential in a niosomal formulation via molecular hybridisation. The cap-que hybrid was synthesised, and its structure was characterised via NMR, FTIR, and HRMS. Niosomes were then loaded with cap-que using the thin-film hydration method. The particle size, polydispersity index, surface charge and drug entrapment efficiency (EE%) of the formulation were 418.8 ± 4.21 nm, 0.393 ± 0.063, 16.25 ± 0.21 mV, and 87.74 ± 2.82%, respectively. The drug release profile showed a sustained release of the active compound (43 ± 0.09%) from the niosomal formulation, compared to the parent drug (80.7 ± 4.68%), over 24 h. The cell viability study confirmed the biosafety of the formulation. The in vivo study in a rat model showed enhanced antihypertensive activity of the hybrid molecule and niosomal formulation which reduced systolic and diastolic pressure when compared to the individual, bare drugs. The findings of this study concluded that the antihypertensive potential of captopril can be enhanced by its hybridisation with quercetin, followed by niosomal nano drug delivery.