Synthetic Derivatives Research Articles

Synthesis of arylated tetrahydrobenzo[H]quinoline-3-carbonitrile derivatives as potential hits for treatment of diabetes.

Aim: Quinoline scaffolds are serving as the core structure for numerous antifungal, analgesic, antipyretic, anti-inflammatory drugs as well as have also been investigated for their potential antidiabetic properties. Though further exploration is required in this area as the current antidiabetic agents, such as acarbose, miglitoland voglibose, are associated with several adverse side effects. In this context, arylated tetrahydrobenzo[H]quinoline-3-carbonitrile derivatives were designed and evaluated as potential antidiabetic agents.Materials & methods: A one-pot multicomponent reaction of 6-methoxy-1-tetralone with ethyl cyanoacetate, ammonium acetateand varying aldehydes yielded a range of new arylated tetrahydrobenzo[h]quinoline-3-carbonitrile molecules 1-36.Results: Compounds 2-5, 12, 13, 19 and 32-34 showed excellent inhibition against α-amylase (IC50=3.42-15.14μM) and α-glucosidase (IC50=0.65-9.23μM) enzymes in comparison to the standard acarbose (IC50=14.35μM). In addition, all compounds revealed significant to moderate DPPH radical scavenging activity (SC50=21.30-138.30μM) compared with BHT (SC50=64.40μM). Kinetic studies confirmed competitive inhibition mode, while molecular docking studies comprehend ligands'interaction with enzyme's active sitesand absorption, distribution, metabolism, and excretion analysis confirms that all synthetic derivatives are nontoxic.Conclusion: This research offers a range of lead candidates to become antidiabetic agents after further advanced study.

Synthetic indole derivatives as an antibacterial agent inhibiting respiratory metabolism of multidrug-resistant gram-positive bacteria.

The survival of modern medicine depends heavily on the effective prevention and treatment of bacterial infections, are threatened by antibacterial resistance. The increasing use of antibiotics and lack of stewardship have led to an increase in antibiotic-resistant pathogens, so the growing issue of resistance can be resolved by emphasizing chemically synthesized antibiotics. This study discovered SMJ-2, a synthetic indole derivative, is effective against all multidrug-resistant gram-positive bacteria. SMJ-2 has multiple targets of action, but the primary mechanism inhibits respiratory metabolism and membrane potential disruption. SMJ-2 was discovered to interfere with the mevalonate pathway, ultimately preventing the synthesis of farnesyl diphosphate, a precursor to the antioxidant staphyloxanthin, eventually releasing reactive oxygen species, and leading phagocytic cells to destroy pathogens. Additionally, no discernible biochemical and histopathological alterations were found in the mouse acute toxicity model. This study emphasizes mechanistic insights into SMJ-2 as a potential antibacterial with an unusual method of action.

Exploring Biological Targets of Magnolol and Honokiol and their Nature-Inspired Synthetic Derivatives: In Silico Identification and Experimental Validation of Estrogen Receptors.

In this work, we describe the results of a computational investigation aimed at identifying potential biological targets of honokiol, magnolol and a series of synthetic prodrug derivatives obtained through esterification of the free hydroxyl groups. The ligand-based and structure-based analyses revealed that these compounds potentially interact with several biological targets, some of which are known while others are new. Honokiol, magnolol, and three of the newly synthesized derivatives may bind to estrogen receptors ERα and ERβ. Biological testing confirmed that these compounds modulate estrogen-regulated transcriptional activity mediated by ERα or ERβ with potencies in the nanomolar range. In particular, magnolol and one of its derivatives (10) behaved as partial antagonists of ERα and ERβ, while compounds 8 and 11 behaved as partial agonists. These findings validate the computational predictions and shed light on the mechanism of action of these natural compounds, paving the way for further investigation in the context of targeted therapies.

Valuable Ca/P Sources Obtained from Tuna Species’ By-Products Derived from Industrial Processing: Physicochemical and Features of Skeleton Fractions

The global tuna canning industry generates substantial volumes of by-products, comprising 50% to 70% of the total processed material. Traditionally, these by-products have been utilized in low-value products such as fish oils and fishmeal. However, there is significant potential to extract high-value compounds from these by-products, such as calcium phosphates (CaP), which can have pharmaceutical, agricultural and biotechnological applications. This work explores the potential of tuna canning by-products, particularly mineral-rich fractions (central skeleton, head and fish bones) as sources of calcium phosphates (CaP), offering a sustainable alternative to conventional synthetic derivatives within a circular bioeconomy framework. By-products from two of the most exploited species (yellowfin and skipjack) were subjected to enzymatic hydrolysis and chemical extraction, followed by controlled calcination to obtain CaP. The content of organic matter, nitrogen, total proteins, lipids and amino acids in the cleaned bones, as well as the main chemical bonds, structure and elemental composition (FT-Raman, XRD, XRF) were evaluated. Results indicated that the highest recovery yield of wet bones was achieved using the chemical method, particularly from the dorsal and caudal fins of yellowfin tuna. The proximal composition, with ash content ranging from 52% to 66% and protein content varying between 30% and 53%, highlights the potential of tuna skeleton substrates for plant growth formulations. Furthermore, variations in crystalline structures of the substrates revealed significant differences depending on the by-product source and species. XRD and Raman results confirmed a monophase calcium phosphate composition in most samples from both species, primarily based on hydroxyapatite (central skeleton, caudal and dorsal fin) or whitlockite/β-tricalcium phosphate (viscera), whereas the heads exhibited a biphasic composition. Comparing the species, yellowfin tuna (YF) exhibited a hydroxyapatite structure in the branchial arch and scales, while skipjack (SKJ) had a biphasic composition in these same regions.

Naturally Occurring Compounds Targeting Peroxisome Proliferator Receptors: Potential Molecular Mechanisms and Future Perspectives for Promoting Human Health

Background: Peroxisome-proliferator-activated receptors (PPARs) constitute nuclear transcription factors controlling gene expression associated with cell growth and proliferation, diverse proteins, lipids, and glucose metabolism, being related to several other pathophysiological states such as metabolic disorders, atherogenesis, carcinogenesis, etc. The present survey aims to analyze the natural compounds that can act as agonists for the PPAR-α, PPAR-β/δ, and PPAR-γ system targeting, highlighting how the amazing biochemical diversity of natural compounds can yield new insights into this “hotspot” of the scientific field. Methods: A narrative review was performed by searching the recent international literature for the last two decades in the most authoritative scientific databases, like PubMed, Scopus, Web of Science, and Embase, using appropriate keywords. Results: Several natural compounds and/or their synthetic derivatives can act as ligands of PPARs, stimulating their transcriptional activity and enabling their use as preventive and/or therapeutic agents for several disease states, such as inflammation, oxidative stress, metabolic disturbances, atherogenesis, and carcinogenesis. Although synthetic compounds are increasingly used as drugs to manage health problems, serious side effects have been observed, while their natural analogues exhibit only few minor side effects. Conclusions: Further clinical studies on natural compounds such as ligands of PPARs and the evaluation of the related molecular mechanisms are needed to implement an effective strategy concerning the pharmaco-technology, food chemistry, and nutrition to introduce them as part of clinical and dietary practice.

Recent Advancements and SAR Studies of Synthetic Coumarins as MAO-B Inhibitors: An Updated Review.

The oxidative deamination of a wide range of endogenous and exogenous amines is catalyzed by a family of enzymes known as monoamine oxidases (MAOs), which are reliant on flavin-adenine dinucleotides. Numerous neurological conditions, such as Parkinson's disease (PD) and Alzheimer's disease (AD), are significantly correlated with changes in the amounts of biogenic amines in the brain caused by MAO. Hydrogen peroxide, reactive oxygen species, and ammonia, among other toxic consequences of this oxidative breakdown, can harm brain cells' mitochondria and cause oxidative damage. The prime objective of this review article was to highlight and conclude the recent advancements in structure-activity relationships of synthetic derivatives of coumarins for MAO-B inhibition, published in the last five years' research articles. The literature (between 2019 and 2023) was searched from platforms like Science Direct, Google Scholar, PubMed, etc. After going through the literature, we have found a number of coumarin derivatives being synthesized by researchers for the inhibition of MAO-B for the management of diseases associated with the enzyme such as Alzheimer's Disease and Parkinson's Disease. The effect of these coumarin derivatives on the enzyme depends on the substitutions associated with the structure. The structure-activity relationships of the synthetic coumarin derivatives that are popular nowadays have been described and summarized in the current study. The results revealed the updated review on SAR studies of synthetic coumarins as MAO-B inhibitors, specifically for Alzheimer's Disease and Parkinson's Disease. The patents reported on coumarin derivatives as MAO-B inhibitors were also highlighted. Recently, coumarins, a large class of chemicals with both natural and synthetic sources, have drawn a lot of attention because of the vast range of biological actions they have that are linked to neurological problems. Numerous studies have demonstrated that chemically produced and naturally occurring coumarin analogs both exhibited strong MAO-B inhibitory action. Coumarins bind to MAO-B reversibly thereby preventing the breakdown of neurotransmitters like dopamine leading to the inhibition of the enzyme A number of MAO-B blockers have been proven to be efficient therapies for treating neurological diseases like Alzheimer's Disease and Parkinson's Disease. To combat these illnesses, there is still an urgent need to find effective treatment compounds.

A synthetic bis-triazine ring derivative based on ammonium phosphonate towards durable flame-retardant modification of cotton fabrics

Cotton is widely used in daily life. However, its flammability limits its application in certain areas. In this study, a novel formaldehyde-free reactive flame retardant, ASBSMP, derived from a bis-triazine ring ammonium phosphonate, was successfully synthesized. The ASBSMP/cotton exhibited excellent flame-retardant properties, with self-extinguishing characteristics and a LIMITING OXYGEN INDEX (LOI) of 41.8%. Even after 50 washing cycles, the LOI remained at a high level of 30.3%, indicating outstanding durability. Thermogravimetric analysis (TGA) revealed its superior thermal stability. Cone calorimeter tests further confirmed the superior flame retardancy of the treated cotton, showing a 44.6% reduction in total heat release (THR) and a 90.1% reduction in peak heat release rate (PHRR) compared to pure cotton. Results from Fourier Transform Infrared Spectroscopy (FTIR), X-ray Photoelectron Spectroscopy (XPS), and char residue analyses demonstrated that ASBSMP exhibited flame-retardant activity in both the gas and condensed phases. ASBSMP/cotton exhibited outstanding mechanical integrity for a wide range of applications.

Design, Synthesis, and Biological Evaluation of Some Novel Retinoid Derivatives

Background: As cancer stands as a significant global health concern, many heterocyclic compounds that are more effective in cancer cells than healthy cells are being investigated for their selective anticancer potentials. One such compound is fenretinide, a synthetic derivative of retinoic acid that has a broad spectrum of cytotoxic activity against primary tumor cells, cell lines, and/or xenografts of various cancers. In this context, bexarotene and its derivatives, synthesized from hybridization of the fenretinide, are expected to possess a potential anticancer activity. Objective: The objective of the present study was to investigate the synthesis of novel amid-derived and bexarotene-based compounds, as well as to assess their cytotoxic effects in different cancer cell lines. Methods: This study involved the synthesis of twelve novel retinoid derivatives (6-17) in a six-step process. The cytotoxic activities of these compounds were assessed against various cancer cell lines, such as A549 (human lung carcinoma), HeLa (human cervical cancer), MCF7 (human breast adenocarcinoma), and WiDr (human colon adenocarcinoma). The chemical structures of these compounds were elucidated through their elemental analysis, mass spectrometry (ESI+, ESI-), as well as 1H-NMR and 13C-NMR spectroscopic data. Results: The obtained cell toxicity results indicated that compounds 6, 8, 11, 12, 13, 14, and 17 were found to exhibit the strongest cytotoxic activity in above mentioned cancer cell lines. The IC50 values for active compounds, 11 and 12, were determined as 2.38μM and 2.29μM, respectively. Remarkably, these compounds displayed higher cytotoxic activity in the WiDr cell line related to positive control, camptothecin (CPT). Moreover, compounds 14 and 17 demonstrated very similar level of cytotoxic activity to CPT, indicating their potential for antitumoral applications upon further studies. Conclusion: While compounds 11, 12, 14, and 17 indicated a very comparable anticancer activity to CPT, compounds 6, 8, 11 and 12 showed more selective anticancer effect against cancer cells than noncancerous cells. In accordance with the findings of the present study, they can be evaluated as primary candidates for further studies, specifically as RXRα-targeted anticancer agents.

Triazole scaffold-based DPP-IV Inhibitors for the management of Type-II Diabetes Mellitus: Insight into Molecular Docking and SAR.

Diabetes mellitus, characterized as a chronic metabolic disorder or a polygenic syndrome; is increasing at a very fast pace among every group of the population worldwide. It arises due to the inability of the body to produce enough insulin (the hormone responsible for controlling blood sugar levels) or inability to utilize the insulin, leading to hyperglycaemic condition, which, if left uncontrolled gives rise to chronic microvascular and macrovascular complications like retinopathy, neuropathy, nephropathy, coronary artery disease, cognitive impairment, etc. Several therapeutic approaches are available for the treatment of diabetes; among which dipeptidyl peptidase (DPP-IV) inhibitors (gliptins) hold a significant place. DPP-IV is a multifunctional enzyme or a serine exopeptidase that plays an imperative role in cleaving bioactive molecules. DPP-IV causes the breakdown of incretin hormone (GLP-1: Glucagon-like peptide 1 and GIP: Glucose-dependent insulinotropic peptide) that is essential for controlling glycaemic levels in the body. Inhibition of DPP-IV enzyme (DPP-IV inhibitors: Sitagliptin, Saxagliptin, Linagliptin, Alogliptin) prevents this breakdown, thereby controlling blood glucose levels and saving the patients from deleterious effects of prolonged hyperglycaemic conditions. Triazole-based DPP-IV inhibitors are a significant class of drugs used to treat Type 2 diabetes mellitus in a dose-dependent manner. Clinical trials have demonstrated their efficacy as monotherapy or in combination with other antidiabetic agents. This review highlights the molecular docking studies and structure-activity relationship of potential synthetic derivatives that may act as lead molecules for future drug discovery and yield drug molecules with enhanced efficacy, potency and reduced toxicity profile.

Isotretinoin-associated chronic diarrhea as a complication of systemic isotretinoin therapy

Objective: Isotretinoin is a synthetic derivative of vitamin A that is highly effective in treating acne vulgaris. Although its common side effects include skin dryness, photosensitivity, epistaxis, and depressive disorders, gastrointestinal side effects should also be considered, though they are less frequently highlighted. Case: We aim to present a 28-year-old female patient who developed chronic diarrhea and associated hypokalemic paralysis during isotretinoin treatment, prescribed for acne management. This case underlines the importance of recognizing gastrointestinal side effects, alongside the more commonly known adverse effects of isotretinoin. Conclusion: Chronic diarrhea is a rare but significant side effect of isotretinoin that may lead to serious complications such as hypokalemic paralysis. In this case, we demonstrated how isotretinoin can cause metabolic imbalances, even in relatively healthy young adults, by inducing diarrhea. While the association between isotretinoin and inflammatory bowel disease remains inconclusive, clinicians should remain vigilant regarding the gastrointestinal side effects of isotretinoin. Early recognition and discontinuation of the drug, combined with appropriate supportive treatments, are essential in preventing further complications. Dermatologists and gastroenterologists should collaborate in identifying patients at higher risk, such as those with pre-existing gastrointestinal conditions, and closely monitor for any adverse effects during isotretinoin treatment. Future studies, particularly large-scale randomized controlled trials, are needed to better understand the relationship between isotretinoin and gastrointestinal side effects.

Potential hepatoprotective properties of synthetic derivatives of thiourea — 2-aminobenzothiazole and IEM-2320

BACKGROUND: Toxic hepatitis is characterized by a significant severity of the course and by high mortality. So, search for effective means of correcting this condition seems to be relevant. It has previously been shown that some thiazolo[5,4-b]indole derivatives are capable to prevent experimental toxic liver damage in laboratory animals. In continuation of this direction, the study of the hepatoprotective properties of synthetic derivatives of thiourea 2-aminobenzothiazole and IEM-2320 was undertaken. AIM: To study the potential hepatoprotective properties of 2-aminobenzothiazole and IEM-2320 in acute carbon tetrachloride poisoning. MATERIALS AND METHODS: Experiments were carried out on 30 male white outbred rats (150–270 g). On a model of carbon tetrachloride poisoning (50% solution of CCl4 in vaseline oil, 0.2 ml/100 g of body weight), the potential hepatoprotective properties of 2-aminobenzothiazole (32 mg/kg) and IEM-2320 (20 mg/kg) were investigated. Ademethionine (Heptral, AbbVie, S.r.L, Italy) at a dose of 20 mg/kg was used as a comparison drug. The studied drugs were administered intraperitoneally 4 times: one hour before the introduction of CCl4, and then — for three subsequent days after the poisoning with CCl4. The results were compared with those of 2 control groups. Animals of the 1st control group were not exposed to CCl4, instead of the studied drugs, they were injected with an equivalent volume of saline solution (0.2 ml/100 g of body weight). Animals of the 2nd control group did not receive any treatment after the CCl4 poisoning. Blood was taken on the seventh day of the experiment. The total contents of protein, glucose, and total cholesterol in blood serum were determined, and the activities of alanine aminotransferase and aspartate aminotransferase were evaluated. RESULTS: Under the CCl4 poisoning, the administration of 2-aminobenzothiazole led to a significant decrease in the concentrations of glucose, total protein, total cholesterol and alanine aminotransferase activity. When IEM-2320 was administered under the condition of poisoning, a decrease in the concentrations of total protein, glucose, urea, total cholesterol, and the alanine aminotransferase activity was observed. CONCLUSIONS: A significant decrease in the biochemical parameters of blood serum after administration of 2-aminobenzothiazole and IEM-2320 under the condition of CCl4 poisoning demonstrates thir potential hepatoprotective properties under acute hepatotropic poisonings.

2α-Methyl-5α-androstan-17β-ol-3-one-17β-heptanoate

Drostanolone is a popular synthetic dihydrotestosterone derivative and an anabolic–androgenic agent which belongs to the steroid class. The crystal structure of a new polymorph of the esterified prodrug of drostanolone, namely drostanolone enanthate, was elucidated using single crystal X-ray diffraction. Furthermore, it was analyzed using the thermal DTA/TGA technique and FT-IR spectroscopy.

Coumarin Derivatives: Pioneering New Frontiers in Biological Applications

Abstract: Coumarins are a vital class of compounds recognized for their significant therapeutic potential, both in their natural forms and as synthetic derivatives. Characterized by a benzene ring fused to an α-pyranose ring, coumarins have garnered considerable attention from the scientific community due to their diverse pharmacological activities. This review article highlights the importance of coumarin hybrids, showcasing their enhanced biological properties and reactivity compared to traditional coumarin structures. We explore the pharmacological profiles of various coumarin derivatives, including their anti-cancer, anti-inflammatory, antiviral, antioxidant, antibacterial, and anti-tuberculosis activities, among others. The review examines how the incorporation of different functional groups on the coumarin scaffold can modulate its effectiveness against various diseases, particularly cancer. Furthermore, we discuss promising results from coumarin-based hybrids, such as coumarinpyridine, coumarin-uracil, and coumarin-quinoline derivatives, demonstrating their efficacy against a range of pathogens. This comprehensive overview serves as a valuable resource for researchers interested in the potential of coumarin derivatives in therapeutic applications.

Inhibitory Effects of Mangifera indica Secondary Metabolites and Their Synthetic Derivatives against SARS-CoV-2 Mpro and NS2B/NS3 (ZIKV and DENV-2).

Chemical studies of Mangifera indica twigs yielded two compounds, identified as taraxerol (1) and methyl gallate (2). The galloyl moiety was suggested as a potential scaffold that can interfere with proteases by previous biological investigations on SARS-CoV-2 main protease (Mpro) inhibitors in combination with docking studies. Therefore, a series of 13 gallate esters were prepared by treating gallic acid with natural and non-natural alcohols. Their inhibitory effects were evaluated against Mpro and NS2B/NS3 of Zika and Dengue viruses. Among the obtained compounds, 2e and 2i were the most potent against Mpro with IC50 values of 2.60 and 4.0 μM, respectively. Compounds 2f and 2g were more potent than others against ZIKV protease with IC50 values of 2.7 and 1.9 μM, respectively. The bioactivity profile against DENV NS2B/NS3 was different with 2e and 2f showing moderate inhibition with IC50 values of 66.0 and 59.29 μM, respectively. It was found that 2f and 2g inhibited ZIKV NS2B/NS3 via a noncompetitive mechanism. The study also showed that 2e and 2f could exert noncompetitive inhibition at the previously described allosteric pocket of flaviviral NS2B/NS3 proteases. Molecular docking revealed different types of interactions among the most prominent were hydrogen bonding with the galloyl moiety.

In vitro and In Silico Molecular Modeling Studies of Newly Synthesized Pyrrole Derivatives for their Antimicrobial and Anticancer Properties

Background: Pyrroles are biologically active scaffolds that can have a number of different effects. They also have unique pharmacophores inside their ring system that make it easier to make molecules that are more active. Significantly, in the past ten years, research has been conducted on the anti-bacterial properties, with a particular emphasis on drug-resistant Gram-positive and Gram-negative pathogens such as mycobacteria. Additionally, scaffolds based on pyrroles were utilized in the production of anti-tumor medicines that function by modulating or suppressing genes. Objective: This research aimed to create new pyrrole derivatives by chemical means and evaluate their antimicrobial and anticancer properties. Methods: By reacting diverse 1H-pyrrole-2-carbohydrazide derivatives with benzaldehyde under normal conditions, a number of pyrrole variations were created. IR, mass spectroscopy, NMR, and elemental analysis were used to characterize the synthesized compounds. The serial dilution method was used to assess antimicrobial activity, along with a molecular docking study against the enzyme α-topoisomerase II (α-Topo II), which effectively controls the topology of DNA. This enzyme is strongly expressed in rapidly dividing cells and is crucial for transcription, replication, and chromosome structure. Pyrrole and its synthetic derivatives are known to exhibit strong anticancer activity by specifically targeting α-Topo II, which has led multiple researchers to investigate α-Topo II inhibitors as potential anticancer medicines. Consequently, designing pyrroline derivatives is interesting since the succinimide portion of the joined heteroaromatic molecule can selectively engage with the ATP binding pocket via the hydrogen bond network. Newer synthesized compounds were also docked via Schrodinger 2022-4 into the active pocket of the three-dimensional crystallographic structure of the ATP site of human topoisomerase IIα (htopo IIα) (PDB ID: 1zxm). Results: Among the newly synthesized pyrrole derivatives, compounds demonstrated significant anti- microbial activity. In addition, the AutoDock Vina application was used to perform in-silico docking computations. Compounds 1a and 1h were found to have a stronger antiproliferative effect than compounds against MCF-07 breast cancer cell linen our study, ligands 1a and 1b exhibited better binding energies of -5.049 and -5.035 kcal/mol, respectively. Most of the synthesized pyrrole derivatives showed promising antiproliferative effects; however, further in vivo investigations are needed to confirm or refute these results. Conclusion: The results of this investigation show that pyrrole derivatives have the potential to be effective antimicrobial and anticancer agents. While resolving safety issues, the structural alterations carried out in this study enhanced the compounds' medicinal capabilities. To clarify the underlying mechanisms of action and enhance the pharmacological characteristics of these new pyrrole derivatives, further research is necessary.

Impairing protein-protein interactions in an essential tRNA modification complex: An innovative antimicrobial strategy against Pseudomonas aeruginosa.

Protein-protein interactions (PPIs) have been recognized as a promising target for the development of new drugs, as proved by the growing number of PPI modulators reaching clinical trials. In this context, peptides represent a valid alternative to small molecules, owing to their unique ability to mimic the target protein structure and interact with wider surface areas. Among the possible fields of interest, bacterial PPIs represent an attractive target to face the urgent necessity to fight antibiotic resistance. Growing attention has been paid to the YgjD/YeaZ/YjeE complex responsible for the essential t6A37 tRNA modification in bacteria. We previously identified an α-helix on the surface of Pseudomonas aeruginosa YeaZ, crucial for the YeaZ-YeaZ homodimer formation and the conserved YeaZ-YgjD interactions. Herein, we present our studies for impairing the PPIs involved in the formation of the YeaZ dimers through synthetic peptide derivatives of this helical moiety, both in vitro with purified components and on P. aeruginosa cells. Our results proved the possibility of targeting those PPIs which are usually essential for protein functioning and thus are refractory to mutational changes and antibiotic resistance development.

Mitochondrial-derived peptides, HNG and SHLP3, protect cochlear hair cells against gentamicin.

Preservation of hair cells is critical for maintaining hearing function, as damage to sensory cells potentially leads to irreparable sensorineural hearing loss. Hair cell loss is often associated with inflammation and oxidative stress. One promising class of bioactive peptides is mitochondrial-derived peptides (MDPs), which have already been proven to protect various tissues from cellular stresses and delay aging processes. Humanin (HN) is one of the best-known members of this family, and recently, we have shown its protective effect in hair cells. The synthetic derivate HN S14G (HNG) has a more potent protective effect than natural HN making it a more useful peptide candidate to promote cytoprotection. A less-known MDP is small humanin-like peptide 3 (SHLP3), which has cytoprotective effects similar to HN, but likely acts through different signaling pathways. Therefore, we examined the effect of exogenous HNG and SHLP3 in auditory hair cells and investigated the molecular mechanisms involved. For this purpose, explants of the organ of Corti (OC) were treated with gentamicin in the presence and absence of HNG or SHLP3. Administration of HNG and SHLP3 reduced gentamicin-induced hair cell loss. The protective mechanisms of HNG and SHLP3 in OC explants included, in part, modulation of AKT and AMPKα. In addition, treatment with HNG and SHLP3 reduced gentamicin-induced oxidative stress and inflammatory gene overexpression. Overall, our data show that HNG and SHLP3 protect hair cells from gentamicin-induced toxicity. This offers new perspectives for the development of therapeutic strategies with MDPs against hearing loss.

Margin constraints and asset prices

Abstract I study the effects of regulatory policy changes on interest rate option prices: margin tightening from the introduction of mandatory interest rate swap clearing by the Dodd–Frank Act in 2010 and margin loosening from the counterbalance of voluntary swaption clearing and synthetic derivatives to the uncleared margin rule in 2016. Employing these variations as exogenous shocks for a quasi-experimental design, I show that swaption prices consistently respond to changes in margin requirements. The results are consistent with theories on the expected margin premium, where the constrained agent holds short positions in zero net supply.

Anti-oxidant and antibacterial activities of novel N-sulfonylphtalimide in an ovalbumin-induced inflammation in Wistar rats.

Phthalimide and N-substituted phthalimide have a special structure that helps them to be pharmaceutically useful and biologically active. In this study, we investigated the antioxidant, anti-inflammatory and antibacterial effects of a synthetic phthalimide-containing derivative in an experimental asthma model. In vitro determination of antioxidant and chelating activity was carried out by spectrophotometric methods. The in vivo antioxidant activity was carried out in Wistar rats sensitized to ovalbumin in the experimental model of asthma. Our results reveal that that the synthesized N-sulfonylphthalimide molecule has a scavenging capacity against the free radical 2,2-diphenyl-1-picryl-hydrazyl (DPPH•) and a chelating activity on ferrous ions and revealed its protective capacity against altered markers of oxidative stress in the experimental asthma model. All the previous results were confirmed by the result of the histopathological study of the liver. Moreover, neo-synthesized N-sulfonylphthalimide 2 showed antibacterial activity against Gram-positive and Gram-negative bacteria with interesting MIC values. Finally, our study highlights the anti-inflammatory, anti-asthmatic and antibacterial effects of the N-sulfonylphthalimide molecule, which could potentially be a drug of choice in asthmatic pathology, especially during bacterial superinfections in the respiratory tract.

Potential Role of Benzoic Acid and its Synthetic Derivatives to Alleviate Cancer: An Up-to-Date Review.

Unregulated cell division is one of the main causes of cancer. These cancerous cells negatively impact nearby healthy cells. Cancer can occur anywhere in the body. Normal cell division occurs when cells grow, reproduce, and divide as the body needs. As a normal cascade of cell growth and division, when the cells get damaged, they undergo death, and normal cells develop. However, sometimes, this process is not followed, and abnormal or damaged cells start to grow and multiply several times more than normal. This particular process may form the basis of cancer. There is a research gap in terms of identifying personalized synthetic anticancer therapy, which may be based on individual patient characteristics with an aim to optimize treatment efficacy and minimize adverse effects. While searching for new bioactive compounds, it has been observed that organic molecules with benzoic acid (BA) moiety possess significant anticancer potential. Several works of literature reported the use of BA from natural or synthetic sources to synthesize bioactive chemicals. It has been observed that several natural products also contain BA moiety, and the presence of this moiety is considered responsible for several important biological activities. Therefore, in order to chemically synthesize a wide variety of potent biologically active compounds, benzoic acid as a basic moiety in the form of a scaffold can be employed. Other synthetic compounds with BA scaffolds include furosemide, tetracaine, and bumetanide. The current article aims to focus on past and present work done on BA derivatives and to emphasize the molecular pathways involved in cancer treatment. The future prospects for research in this area are encouraging as researchers are striving to advance synthetic BA derivatives. This could possibly contribute to more efficient treatments and better results for cancer patients.