Bioactive Derivatives Research Articles

Small gold nanoparticles for tandem cyclization/reduction and cyclization/hydroalkoxylation reactions

With peculiar structural features at the surface of small metal nanoparticles, some discrete sites can display catalytic behaviour similar to what could be observed with mononuclear metal catalysts in solution. We have studied the transfer of two catalytic tandem reactions from homogeneous to heterogeneous conditions. Tandem cyclisation/reduction of ortho-alkynyl benzaldehyde derivatives was successfully achieved with Au nanoparticles over TiO2 (Au NPs/TiO2) in the presence of Hantzsch ester with 45-98% yields for 15 examples (average yield: 70.4%). Similarly, tandem cyclisation/hydroalkoxylation of ortho-alkynyl benzaldehyde derivatives was successfully achieved with Au NPs/TiO2 in methanol or other alcohols with 62-96% yields for 17 examples (average yield: 84.9%). The application potential of this catalytic system was demonstrated with the total synthesis of a bioactive isochromene derivative featuring one of the developed reactions as the key step and the implementation of the tandem cyclisation/hydroalkoxylation in a continuous flow reactor, scaling up the reaction by a factor of 10 without loss of efficiency.

Carob seeds as a source of bioactive flavonoid derivatives: isolation, network pharmacology-guided anti-cancer activity, and HPLC standardization.

Carob, Ceratonia siliqua L. (CS), is a legume well-known for its edible pod pulp. Its seeds are used almost exclusively as a source of the food additive E410. Although a variety of metabolites have been identified by HPLC and LC-MS analysis in CS,reports concerned with their isolation are scarce. Methodology:In this study, two flavonoid derivatives were isolated from the methanolic extract of CS seeds, namely, quercetin-3-O-rhamnosideand 4'-p-hydroxybenzoylisorhamnetin-3,7-di-O-rhamnoside.Network pharmacology was unusually used as a guide for estimation of the biological potential of the isolated compounds. Finally, the methanolic extract of CS seeds and its ethyl acetate fraction were standardized for their 4'-p-hydroxybenzoylisorhamnetin-3,7-di-O-rhamnoside content by HPLC. The identified isolates displayed the ability to interfere with the activity of several target proteins associated with renal and colon cancers.Their cytotoxic effect on renal and colorectal cancer cell lines was investigated in comparison to Doxorubicin. The selectivity of the isolated compounds was evaluated on normal human fetal fibroblast cell lines. The isolated 4'-p-hydroxybenzoylisorhamnetin-3,7-di-O-rhamnoside showed very potent cytotoxic activity against the tested cell lines with the highest selectivity. CS seeds can be used as a source of bioactive flavonoid derivatives that can be incorporated in pharmaceutical industries.

Seagrass Meadows: Prospective Candidates for Bioactive Molecules.

Seagrass meadows consist of angiosperms that thrive fully submerged in marine environments and form distinct ecosystems. They provide essential support for many organisms, acting as nursery grounds for species of economic importance. Beyond their ecological roles, seagrasses and their associated microbiomes are rich sources of bioactive compounds with the potential to address numerous human healthcare challenges. Seagrasses produce bioactive molecules responding to physical, chemical, and biological environmental changes. These activities can treat microbe-borne diseases, skin diseases, diabetes, muscle pain, helminthic diseases, and wounds. Seagrasses also offer potential secondary metabolites that can be used for societal benefits. Despite numerous results on their presence and bioactive derivatives, only a few studies have explored the functional and therapeutic properties of secondary metabolites from seagrass. With the increasing spread of epidemics and pandemics worldwide, the demand for alternative drug sources and drug discovery has become an indispensable area of research. Seagrasses present a reliable natural source, making this an opportune moment for further exploration of their pharmacological activities with minimal side effects. This review provides a comprehensive overview of the biochemical, phytochemical, and biomedical applications of seagrasses globally over the last two decades, highlighting the prospective areas of future research for identifying biomedical applications.

Comprehensive Review of Phytochemical Studies and Legalization of Cannabis in Morocco

Research on cannabis and its bioactive derivatives, including cannabinoids, non-cannabinoids, and extracts, has significantly increased in recent years due to their potential therapeutic applications as demonstrated by numerous published studies. Although there is evidence of the potential efficacy of cannabinoid and non-cannabinoid compounds from cannabis in the treatment of various diseases and syndromes, further research is required to mitigate the potential damage that could result from the excessive use of cannabinoid products, particularly tetrahydrocannabinol (THC), such as psychotropic effects, addiction, cognitive deficits, cardiovascular problems, and impacts on mental health. This review describes phytochemical and biological studies on cannabis grown in Morocco, utilizing databases such as SciFinder, ScienceDirect, Scopus, Google Scholar, and PubMed to provide updated data on cannabis in Morocco. The findings of this research aim to enable investors, economic operators, researchers, and policymakers to better understand the current state of cannabis in Morocco, thereby promoting industry growth and cannabis-related innovation. Additionally, this paper includes a brief discussion on the legalization of cannabis in Morocco, highlighting the new opportunities for investment in medical cannabis. This study also underscores that much remains to be explored regarding Moroccan cannabis, from the isolation of bioactive compounds and pre-clinical studies to clinical trials and the mass production of approved cannabis-based medicines. Furthermore, the findings are intended to inform key stakeholders about the current state of cannabis in Morocco, fostering industry growth and innovation.

Isochromophilones H-K, the new bioactive azaphilone derivatives isolated from fungal strain Diaporthe perseae associated with Pongamia pinnata plant

The phytochemical study of the Diaporthe species has revealed significant classes of mycotoxins and phomopsins. Dihydroanthracenone derivatives, chromanones and isochromophilones have also been isolated from Diaporthe sp. These findings led us to explore the Diaporthe perseae for phytochemical analysis that resulted in the isolation of four new compounds designated as isochromophilones H-K (1–4), alongside three previously identified metabolites. Using extensive spectroscopic investigations such as NMR, and Mass spectroscopy, their structures were elucidated. Furthermore, the antimicrobial and anti-diabetic potentials of all isolated compounds were assessed. Compounds 1–3 demonstrated significant antibacterial activity, while compounds 4–7 exhibited comparatively lower effectiveness than the reference antibiotics. Compounds 2–3 showed potent diabetic inhibition, displaying IC50 values of 16.3 ± 0.3 and 25.4 ± 0.3, respectively. Compounds 1, 5, and 6 displayed mild anti-diabetic effects, with IC50 values of 56.5 ± 0.8, 37.6 ± 0.4, and 48.2 ± 0.6. However, compounds 4 and 7 were found least active.

Electrochemical Oxidative Functionalization of Pyrazolin‐5‐ones: Access to 4‐Quinoxalinone‐Substituted Pyrazoles

A strategy for the preparation of 4‐quinoxalinone‐substituted pyrazole derivatives by electrochemical functionalization of pyrazolin‐5‐ones is reported. Quinoxalinones, possessing significant biological activities, serve as aryl sources and participate in the transformation under electrochemical conditions without the necessity of adding extra oxidants and catalysts. This method features one‐pot synthesis, scale‐up and late‐stage functionalization of bioactive molecule derivatives. Notably, activity testing reveals that some compounds exhibit superior inhibitory effects on the proliferation of A549 cells compared to 5‐fluorouracil.

Exploring the binding interaction of Bis-benzimidazoles with BSA and relocation of bound drug from BSA to DNA

In recent years Bis-benzimidazole derivatives have gained much research interest due to their regulatory role in biological reactions to control diseases. Therefore, probing the interaction of the bioactive derivatives with biomolecules is crucial for both physiological and pharmacological aspects. Consequently, we studied the interaction between Bis-benzimidazoles and bovine serum albumin (BSA) as model transport protein by multi-spectroscopic techniques. It was also evident that substitutions of the phenolic OH group of Hoechst-33258 by -OMe and -NEt2 group have negligible impact on the binding phenomenon with BSA. Additionally, we have shown that the bound derivatives can be successfully relocated from serum albumin to calf-thymus DNA (ct-DNA). The observed higher binding affinity of the Hoechst-33258 to ct-DNA than BSA was responsible for the relocation of dyes from BSA to DNA. The competitive displacement assay with known site markers revealed that the probable binding location of the Hoechst-33258 within the serum protein was site IB. Molecular docking study was also performed to support the experimental findings and to obtain the possible interaction of drug molecule in the protein environment. Our findings might be helpful in overcoming the challenges associated with the delivery of bis-benzimidazole derivatives.

Modular and Diverse Synthesis of Acrylamides by Palladium-Catalyzed Hydroaminocarbonylation of Acetylene.

The development of all kinds of covalent drugs had a major impact on the improvement of the human health system. Covalent binding to target proteins is achieved by so-called electrophilic warheads, which are incorporated in the respective drug molecule. In the last decade, specifically acrylamides emerged as attractive warheads in covalent drug design. Herein, a straightforward palladium-catalyzed hydroaminocarbonylation of acetylene has been developed, allowing a modular and diverse synthesis of bio-active acrylamides. This general protocol features high atom efficiency, wide functional group compatibility, high chemoselectivity and proceeds additive free under mild reaction conditions. The synthetic utility of this protocol is showcased in the synthesis of ibrutinib, osimertinib, and other bio-active compound derivatives.

Recent Advances in Transition Metal Catalyzed Synthesis of C3-Substitution-free 2-Oxindole Derivatives

Abstract: 2-Oxindole unit is one of the most important scaffolds found in several alkaloids, natural products, antitumor agents, pharmaceutically important compounds, etc. Molecules containing the 2- oxindole moiety were first isolated from the cat claw plant, widely distributed in the Amazon jungle. It has now been demonstrated that these molecules are present in a wide range of chemicals derived from plant sources. The capacity of 2-oxindole to be altered by various chemical groups to provide unique biological activities can be attributed to its function as a chemical framework for creating and developing biological medications. Since the development of its first synthetic methodology, several research groups have developed protocols for producing 2-oxindole core and its bioactive derivatives. These include the traditional method and the transition/non-transition metal-catalyzed pathway for the synthesis of C3-non-substituted/C3-mono-substituted/C3-di-substituted core. Among those, C3-substitution-free 2-oxindole core synthesis is quite a challenging task, as C3-centre is very reactive. Syntheses of C3-substitution-free 2-oxindole cores have been less explored compared to other substituted 2-oxindole derivatives. In this review article, we have mainly focused on showcasing the transition metal-catalyzed synthetic methodology for the synthesis of 2-oxindoles with no substitution at C3-centre.

A Deep Mining Strategy for Peptide Rapid Identification in Lactobacillus reuteri Based on LC-MS/MS Integrated with FBMN and De Novo Sequencing.

Lactobacillus reuteri (L. reuteri) is widely recognized as a probiotic that produces prebiotics. However, studies on bioactive peptides or amino acid (AA) derivatives produced by L. reuteri are still lacking, whereas many bioactive peptides and AA derivatives have been found in other Lactobacillus species. In addition, rapid identification of peptides is challenged by the large amount of data and is limited by the coverage of protein databases. In this study, we performed a rapid and thorough profile of peptides in L. reuteri incorporating Global Natural Products Social Molecular Networking (GNPS) platform database searching, de novo sequencing, and deep mining, based on feature-based molecular networking (FBMN). According to FBMN, it was found that peptides containing identical or similar AA compositions were grouped into the same clusters, especially cyclic dipeptides (CDPs). Therefore, the grouping characteristics of clusters, differences in precursor ions, and characteristic fragment ions were utilized for the mining of deeply unknown compounds. Through this strategy, a total of 192 compounds, including 184 peptides, were rapidly identified. Among them, 53 CDPs, including four novel ones, were found for the first time in L. reuteri. Then, one of the novel CDPs, cyclo(5-OMe-Glu-4-OH-Pro), was isolated and characterized, which was consistent with the identification results. Moreover, some of the identified peptides exhibited considerable interactions with seven anti-inflammatory-related target proteins through molecular docking. According to the binding energies of peptides with different AA consistencies, it was considered that the existence of unnatural AAs in CDPs might contribute to their anti-inflammatory activity. These results provide a valuable strategy for the rapid identification of peptides, including CDPs. This study also reveals the substance basis for the potential anti-inflammatory effects exerted by L. reuteri.

Synthesis of 3-Methyleneisoindolin-1-ones via Rhodium(III)-Catalyzed C-H/N-H Activation and Annulation of N-Methoxybenzamides with Potassium Vinyltrifluoroborate.

Isoindolinones are vital heterocyclic compounds in medicinal chemistry, notable for their diverse bioactivities. Significant attention has been devoted to their preparation; however, existing methods are unsuitable for constructing unsubstituted 3-methyleneisoindolin-1-ones. Herein, we present a rhodium(III)-catalyzed method for synthesizing unsubstituted 3-methyleneisoindolin-1-ones via C-H/N-H activation and annulation of N-methoxybenzamides with potassium (ethenyl)trifluoroborate. This approach offers mild reaction conditions, high regioselectivity, and efficient yields. Interestingly, sterically demanding or heterocyclic N-methoxyaromaticamides resulted in the formation of 2-vinyl(hetero)aromatic amides instead of 3-methyleneisoindolin-1-ones. Mechanistic insights suggest a rhodacycle intermediate pathway, highlighting the method's potential for developing new bioactive isoindolinone derivatives.

Identification of Fatty Acids, Amides and Cinnamic Acid Derivatives in Supercritical-CO2 Extracts of Cinnamomum tamala Leaves Using UPLC-Q-TOF-MSE Combined with Chemometrics.

Cinnamomum tamala leaf (CTL), also known as Indian bay leaf, is used all over the world for seasoning, flavoring, and medicinal purposes. These characteristics could be explained by the presence of several essential bioactive substances and lipid derivatives. In this work, rapid screening and identification of the chemical compounds in supercritical (SC)-CO2 extracts of CTL by use of UPLC-Q-TOF-MSE with a multivariate statistical analysis approach was established in both negative and positive mode. A total of 166 metabolites, including 66 monocarboxylic fatty acids, 52 dicarboxylic fatty acids, 27 fatty acid amides, and 21 cinnamic acid derivatives, were tentatively identified based on accurate mass and the mass spectrometric fragmentation pattern, out of which 142 compounds were common in all SC-CO2 extracts of CTL. Further, PCA and cluster hierarchical analysis clearly discriminated the chemical profile of analyzed extracts and allowed the selection of SC-CO2 extract rich in fatty acids, fatty acid amides, and other bioactive constituents. The result showed that the higher number of compounds was detected in CTL4 (300 bar/55 °C) extract than the other CTL extracts. The mono- and di-carboxylic fatty acids, fatty acid amides, and cinnamic acid derivatives were identified in CTL for the first time. UPLC-Q-TOF-MSE combined with chemometric analysis is a powerful method to rapidly screen the metabolite profiling to justify the quality of CTL as a flavoring agent and in functional foods.

Tetrahydroisoquinoline reduces angiogenesis by interacting myeloma cells with HUVECs mediated by extracellular vesicles.

Multiple myeloma (MM) is a neoplastic condition resulting from the uncontrolled expansion of B-cell-derived plasma cells. The importance of angiogenesis in MM development has also been demonstrated. Extracellular vesicles (EVs) have vital functions in interactions between neighboring cells, such as angiogenesis. The objective of this in vitro study was to examine the transfection and angiogenesis effects of MM-EVs on endothelial cells (ECs) upon treatment with Tetrahydroisoquinoline (THIQ) as a bioactive organic compound derivative from isoquinoline. Following treatment of multiple myeloma cells (U266) with THIQ, MM-EVs were harvested and transmigrated to human umbilical vein endothelial cells (HUVEC) in a co-culture model. EVs transmigration was traced by flow cytometry. Correspondingly, the expression of angiogenic genes and/or proteins in U266 cells and HUVECs was measured by RT-PCR and ELISA methods. Likewise, the proliferation and migration of HUVECs treated with THIQ-treated MM-EVs were visualized and estimated by performing both tube formation and scratch wound healing methods. Surprisingly, the anti-angiogenic effect of THIQ-treated MM-EVs was evident by the decreased expression of CD34, VEGFR2, and IL-6 at the mRNA and/or protein levels after internalization of MM-EVs in HUVEC. Finally, tube formation and scratch wound healing experiments showed inhibition of HUVEC cell proliferation and migration by THIQ-treated MM-EVs compared to control MM-EVs. MM-EVs derived from THIQ-treated myeloma cells (U266) inhibited angiogenesis in HUVECs. This phenomenon is coordinated by the internalized THIQ-treated MM-EVs in HUVECs, and ultimately the reduction of angiogenic factors and inhibition of tube formation and scratch wound healing.

Photoredox-Catalyzed Amino-Radical-Transfer-Mediated Three-Component Alkylarylation of Alkenes.

We herein reported a novel photoredox-catalyzed three-component alkylarylation of vinyl arenes with alkylboronic pinacol esters (APEs) and cyanoarenes via radical addition/cross-coupling to construct 1,1-diarylalkanes. In this transformation, alkyl radicals were easily available by visible-light-induced oxidative N-H cleavage of morpholine, which used APEs as a radical precursor. Furthermore, this protocol exhibited a broad substrate scope, enabling various styrenes, APEs, and cyanoarenes, as well as bioactive molecule derivatives.

One-Pot Synthesis and Computational Investigation of New Bioactive Chromene Derivatives

One-Pot Synthesis and Computational Investigation of New Bioactive Chromene Derivatives

Functionalized Palygorskite as a Delivery Platforms for Bioactive Asymmetric Beta-Diketone Dyes

Natural clay minerals are among the most versatile materials used in the biomedical field. Palygorskite has found various applications in this field, from the treatment of diarrheal diseases in the past to materials with antibacterial properties and platforms carrying bioactive compounds used in the treatment of diseases, cosmetic and healthcare products in the present. In this study, a possible delivery method of some bioactive asymmetric β-diketonic compounds is presented. Palygorskite modified with amphionic groups (P) and copper ions (PCu) was used as a platform to load bioactive curcumin derivatives (1 and 2). By varying the copper ions, the amounts of charged active compounds were monitored. Studies have shown that the hybrid materials resulting from the loading of 1 and 2 compounds on palygorskite with 30% copper ions (PCu30) can be used as delivery methods for these asymmetric curcumin derivatives, while palygorskite with 50% copper ions(PCu50) loaded with the same type of bioactive compounds has antibacterial properties.

Isatin-based ibuprofen and mefenamic acid Schiff base derivatives as dual inhibitors against urease and α–glucosidase: In vitro, in silico and cytotoxicity studies

α-Glucosidase and urease inhibitors have emerged as crucial for developing therapeutic drugs targeting diabetes and gastrointestinal disorders. This study reports on new series of ibuprofen and mefenamic acid Schiff base derivatives incorporating isatin as dual inhibitors of α-glucosidase and urease enzymes. These synthesized derivatives (7a-r) were structurally characterized by 1H NMR, 13C NMR and HRMS (EI). Biological evaluation (IC50) identified several derivatives i.e.,7a (urease = 17.37 ± 1.37 µM, α-glucosidase = 44.1 ± 1.15 µM), 7j, (urease = 16.61 ± 1.37 µM, α-glucosidase = 81.2 ± 1.33 µM), 7o, (urease = 18.63 ± 1.27 µM, α-glucosidase = 70.3 ± 1.14 µM), 7r (urease = 11.36 ± 1.32 µM, α-glucosidase = 39.3 ± 1.17 µM), as dual inhibitors of urease (thiourea 21.37 ± 1.76 µM) and α–glucosidase (acarbose 375.82 ± 1.76 µM) enzymes. These bioactive derivatives were explored for cell viability studies against mononuclear cells revealing a good cytocompatibility. In silico molecular docking studies were also conducted to predict the binding mode of new derivatives with target enzymes that were found consistent with the results of in vitro research.

Identification of mitochondrial ATP synthase as the cellular target of Ru-polypyridyl-β-carboline complexes by affinity-based protein profiling.

Ruthenium polypyridyl complexes are promising anticancer candidates, while their cellular targets have rarely been identified, which limits their clinical application. Herein, we design a series of Ru(II) polypyridyl complexes containing bioactive β-carboline derivatives as ligands for anticancer evaluation, among which Ru5 shows suitable lipophilicity, high aqueous solubility, relatively high anticancer activity and cancer cell selectivity. The subsequent utilization of a photo-clickable probe, Ru5a, serves to validate the significance of ATP synthase as a crucial target for Ru5 through photoaffinity-based protein profiling. Ru5 accumulates in mitochondria, impairs mitochondrial functions and induces mitophagy and ferroptosis. Combined analysis of mitochondrial proteomics and RNA-sequencing shows that Ru5 significantly downregulates the expression of the chloride channel protein, and influences genes related to ferroptosis and epithelial-to-mesenchymal transition. Finally, we prove that Ru5 exhibits higher anticancer efficacy than cisplatin in vivo. We firstly identify the molecular targets of ruthenium polypyridyl complexes using a photo-click proteomic method coupled with a multiomics approach, which provides an innovative strategy to elucidate the anticancer mechanisms of metallo-anticancer candidates.

A Review on Indole-triazole Molecular Hybrids as a Leading Edge in Drug Discovery: Current Landscape and Future Perspectives.

Molecular hybridization is a rational design strategy used to create new ligands or prototypes by identifying and combining specific pharmacophoric subunits from the molecular structures of two or more known bioactive derivatives. Molecular hybridization is a valuable technique in drug discovery, enabling the modulation of unwanted side effects and the creation of potential dual-acting drugs that combine the effects of multiple therapeutic agents. Indole-triazole conjugates have emerged as promising candidates for new drug development. The indole and triazole moieties can be linked through various synthetic strategies, such as click chemistry or other coupling reactions, to generate a library of diverse compounds for biological screening. The achievable structural diversity with indole-triazole conjugates offers avenues to optimize their pharmacokinetic and pharmacodynamic attributes, amplifying their therapeutic efficacy. Researchers have extensively tailored both indole and triazole frameworks with diverse modifications to comprehend their impact on the drug's pharmacokinetic and pharmacodynamic characteristics. The current review article endeavours to explore and discuss various research strategies to design indoletriazole hybrids and elucidate their significance in a variety of pathological conditions. The insights provided herein are anticipated to be beneficial for the researchers and will likely encourage further exploration in this field.

Systematic Review on Major Antiviral Phytocompounds from Common Medicinal Plants against SARS-CoV-2.

Viral infections are rising around the globe and with evolving virus types and increasing varieties of viral invasions; the human body is developing antimicrobial resistance continuously. This is making the fight of mankind against viruses weak and unsecured. On the other hand, changing lifestyle, globalization and human activities adversely affecting the environment are opening up risks for new viral predominance on human race. In this context the world has witnessed the pandemic of the human Coronavirus disease (COVID-19) recently. The disease is caused by the Coronavirus namely Severe Acute Respiratory Syndrome Coronavirus 2 (SARSCoV- 2). Developing potential and effective vaccine is also time consuming and challenging. The huge resource of plants around us has rich source of potent antiviral compounds. Some of these molecules may serve as tremendously potent lead molecules whose slight structural modifications may give us highly bioactive antiviral derivatives of phytocompounds. Every geographical region is rich in unique plant biodiversity and hence every corner of the world with rich plant biodiversity can serve as abode for potential magical phytocompounds most of which have not been extensively explored for development of antiviral drug formulations against various viruses like the HIV, HPV etc., and the Coronavirus, also known as SARS-CoV-2 which causes the disease COVID-19. Several phytocompounds from various medicinal plants have already been screened using in silico tools and some of them have yielded promising results establishing themselves as potent lead molecules for development of drugs against the highly mutating SARS-CoV-2 virus and thus these phytocompounds may be beneficial in treating COVID-19 and help human to win the life threatening battle against the deadly virus. The best advantage is that these phytocompounds being derived from nature in most of the cases, come with minimum or no side effects compared to that of chemically synthesized conventional bioactive compounds and are indigenously available hence are the source of cost effective drug formulations with strong therapeutic potentials.