Indole Group Research Articles

Tris(pyridin‐2‐ylmethyl)amine‐Based Ion Pair Receptors for Selective Lithium Salt Recognition

AbstractTripodal ion pair receptors 1 and 2 consisting of tris(pyridine‐2‐ylmethyl)amine as a cation binding site linked with nitrophenyl urea or amidonitroindole groups as anion binding motifs have been synthesized. 1H NMR spectroscopic analyses carried out in 10 % DMSO in acetonitrile revealed that both ion pair receptors 1 and 2 are able to bind the LiCl ion pair with high selectivity over NaCl, KCl, RbCl, and CsCl. 1H NMR spectroscopic analyses in combination with molecular mechanics calculations proved that the lithium cation is bound to the tris(pyridin‐2‐ylmethyl)amine subunit while the chloride anion interacts with the NHs of urea or amido indole groups via hydrogen bonds. The addition of fluoride to the lithium cation complexes of receptors 1 and 2 leads to the release of the lithium cation from the receptors whereas chloride and bromide are co‐bound with lithium forming LiCl and LiBr ion pair complexes, respectively. The affinity of receptor 1 for the lithium cation was found to be improved by 5.0‐fold when the counter anion of Cl− is co‐bound within the receptor.

Palladium-Catalyzed Three-Component Cross-Coupling of Conjugated Dienes with Indoles Using Ethynylbenziodazolones as Electrophilic Alkynylating Reagents.

A palladium-catalyzed regioselective 1,2-alkynyl-carbonalization of conjugated dienes with ethynylbenziodazolone (EBZ) and indoles has been developed for the first time. Various molecules containing alkenyl, alkynyl, and indole groups were readily obtained. Moreover, the resulting products can be applied to various derivatizations. This protocol uses EBZ as an electrophilic alkynylating reagent, avoiding the byproduct of dimerization of alkynes.

Cation–π interaction assisted facile preparation of graphene/epoxy nanocomposites with superior strength and toughness

AbstractHigh‐performance graphene/epoxy nanocomposites are desired in many fields. However, the performance of graphene/epoxy nanocomposites is far from the actual demand, and many methods reported for the preparation of graphene/epoxy nanocomposites need the participation of environmentally harmful organic solvents. Herein, a novel, facile, and green cation–π interaction assisted phase transfer approach is developed for construction of graphene/epoxy nanocomposites. This strategy includes constructing potassium ion modified reduce graphene oxide (K‐rGO) as nanofiller and choosing 1‐(oxiran‐2‐ylmethyl)‐1H‐indole (IN) as phase transfer agent. The cation–π interaction is formed between K‐rGO and indole group, which not only facilitates the transfer of K‐rGO from water phase to organic phase, but also enhances the dispersion of K‐rGO in epoxy. When the loading of K‐rGO is 0.10 wt%, the tensile strength and elongation at break of epoxy nanocomposites increase by 116.6% and 126.5%, respectively, compared to neat epoxy. The simultaneous improvement in tensile strength and extensibility of graphene/epoxy nanocomposites is achieved. Furthermore, the prepared epoxy nanocomposites exhibit an excellent thermal conductivity owing to the good dispersion of K‐rGO in epoxy matrix.

Fluorescent behavior of melatonin and related indoleamines in natural deep eutectic solvents

Melatonin is a natural hormone produced by the pineal gland and generated as a special metabolite in plants from tryptophan as a precursor and serotonin as an intermediate. These indoleamines show intrinsic fluorescence properties due to the presence of the indole group in their chemical structure, which made them suitable for the analysis by fluorescence-based techniques. In this research, it is described the first comprehensive study of the fluorescence of melatonin and its indole derivatives in several natural deep eutectic solvents (NADES). As melatonin exhibits solvent-dependent fluorescence characteristics, we have measured the quantum yields of the molecules in NADES and conventional solvents with the purpose of understanding the fluorescent behavior in these solvents that will offer a new alternative to conventional medium. The results showed differential fluorescence behavior of melatonin and its metabolic precursors in NADES that could be explained in terms of each fluorophore structure and potential hydrogen bond interactions with eutectic systems. Finally, the turn-off observed for melatonin in the NADES system based on fructose-citric acid and water could inspire the development of new analytical approaches.

Synthesis and Hydrogelation of Star-Shaped Graft Copolypetides with Asymmetric Topology.

To study the self-assembly and hydrogel formation of the star-shaped graft copolypeptides with asymmetric topology, star-shaped poly(L-lysine) with various arm numbers were synthesized by using asymmetric polyglycerol dendrimers (PGDs) as the initiators and 1,1,3,3-tetramethylguanidine (TMG) as an activator for OH groups, followed by deprotection and grafting with indole or phenyl group on the side chain. The packing of the grafting moiety via non-covalent interactions not only facilitated the polypeptide segments to adopt more ordered conformations but also triggered the spontaneous hydrogelation. The hydrogelation ability was found to be correlated with polypeptide composition and topology. The star-shaped polypeptides with asymmetric topology exhibited poorer hydrogelation ability than those with symmetric topology due to the less efficient packing of the grafted moiety. The star-shaped polypeptides grafted with indole group on the side chain exhibited better hydrogelation ability than those grafted with phenyl group with the same arm number. This report demonstrated that the grafted moiety and polypeptide topology possessed the potential ability to modulate the polypeptide hydrogelation and hydrogel characteristics.

Drug design and DNA structural research inspired by the Neidle laboratory: DNA minor groove binding and transcription factor inhibition by thiophene diamidines

The understanding of sequence-specific DNA minor groove interactions has recently made major steps forward and as a result, the goal of development of compounds that target the minor groove is an active research area. In an effort to develop biologically active minor groove agents, we are preparing and exploring the DNA interactions of diverse diamidine derivatives with a 5′-GAATTC-3′ binding site using a powerful array of methods including, biosensor-SPR methods, and X-ray crystallography. The benzimidazole-thiophene module provides an excellent minor groove recognition component. A central thiophene in a benzimidazole-thiophene-phenyl aromatic system provides essentially optimum curvature for matching the shape of the minor groove. Comparison of that structure to one with the benzimidazole replaced with an indole shows that the two structures are very similar, but have some interesting and important differences in electrostatic potential maps, the DNA minor groove binding structure based on x-ray crystallographic analysis, and inhibition of the major groove binding PU.1 transcription factor complex. The binding KD for both compounds is under 10 nM and both form amidine H-bonds to DNA bases. They both have bifurcated H-bonds from the benzimidazole or indole groups to bases at the center of the -AATT- binding site. Analysis of the comparative results provides an excellent understanding of how thiophene compounds recognize the minor groove and can act as transcription factor inhibitors.

Concerted and Stepwise Proton-Coupled Electron Transfer for Tryptophan-Derivative Oxidation with Water as the Primary Proton Acceptor: Clarifying a Controversy

Concerted electron-proton transfer (CEPT) reactions avoid charged intermediates and may be energetically favorable for redox and radical-transfer reactions in natural and synthetic systems. Tryptophan (W) often partakes in radical-transfer chains in nature but has been proposed to only undergo sequential electron transfer followed by proton transfer when water is the primary proton acceptor. Nevertheless, our group has shown that oxidation of freely solvated tyrosine and W often exhibit weakly pH-dependent proton-coupled electron transfer (PCET) rate constants with moderate kinetic isotope effects (KIE ≈ 2–5), which could be associated with a CEPT mechanism. These results and conclusions have been questioned. Here, we present PCET rate constants for W derivatives with oxidized Ru- and Zn-porphyrin photosensitizers, extracted from laser flash-quench studies. Alternative quenching/photo-oxidation methods were used to avoid complications of previous studies, and both the amine and carboxylic acid groups of W were protected to make the indole the only deprotonable group. With a suitably tuned oxidant strength, we found an ET-limited reaction at pH < 4 and weakly pH-dependent rates at pH > ∼5 that are intrinsic to the PCET of the indole group with water (H2O) as the proton acceptor. The observed rate constants are up to more than 100 times higher than those measured for initial electron transfer, excluding the electron-first mechanism. Instead, the reaction can be attributed to CEPT. These conclusions are important for our view of CEPT in water and of PCET-mediated radical reactions with solvent-exposed tryptophan in natural systems.

3-Alkynylindoles as Building Blocks for the Synthesis of Electronically Tunable Indole-Based Push-Pull Chromophores.

In this study, two different classes of push–pull chromophores were synthesized in modest to excellent yields by formal [2+2] cycloaddition-retroelectrocyclization (CA-RE) reactions. N-Methyl indole was introduced as a new donor group to activate alkynes in the CA-RE transformations. Depending on the side groups’ size and donor/acceptor characteristics, N-methyl indole-containing compounds exhibited λmax values ranging between 378 and 658 nm. The optoelectronic properties of the reported D–A-type structures were studied by UV/vis spectroscopy and computational studies. The complete regioselectivity observed in the products was elaborated by one-dimensional (1D) and two-dimensional (2D) NMR studies, and the electron donor strength order of N-alkyl indole and triazene donor groups was also established. The intramolecular charge-transfer characteristics of the target push–pull chromophores were investigated by frontier orbital depictions, electrostatic potential maps, and time-dependent density functional theory calculations. Overall, the computational and experimental results match each other. Integrating a new donor group, N-alkyl indole, into the substrates used in formal [2+2] cycloaddition-retroelectrocyclizations has significant potential to overcome the limited donor-substituted substrate scope problem of CA-RE reactions.

Tough non-covalent adaptable networks: Cation-π cross-linked rigid epoxy

Polymeric materials containing dynamic crosslinks and adaptable networks have obscured the line between the “thermosets” and “thermoplastics”, since they are able to be reprocessed or welded while being permanently cross-linked at the same time. However, it is still a great challenge to combine the good mechanical properties and excellent dynamic properties. Herein, cation-π interactions between indole groups and Eu3+ were applied as cross-links in rigid networks of thermosetting epoxy to form tough non-covalent adaptable networks (NANs). The cation-π cross-linked epoxy exhibited outstanding solvent resistance and excellent mechanical properties with the tensile strength of 38 MPa, while the glass transition temperature (Tg) was up to 87 °C. Moreover, the cross-linked epoxy could be readily reprocessed and welded at moderate temperature of 120 °C, while the tensile strength recovered to 32 MPa after recycling. Meanwhile, the epoxy exhibited other dynamic properties including triple shape memory and tension triggered fluorescence. The readily prepared cation-π cross-linked epoxy provides a general way to develop tough NANs with high performance and excellent dynamic properties, which may be suitable for other non-covalent dynamic bonds and thermosetting matrix.

Diindolylmethane ameliorates platelet aggregation and thrombosis: In silico, in vitro, and in vivo studies

Diindolylmethane (DIM), a major metabolite of indole-3-carbinol (I3C), plays a vital role in the pharmacological actions of I3C. The role of DIM in the inhibition of platelet aggregation and thrombus generation is yet to be revealed. However, how DIM and I3C modulate the interaction of platelets with the glycoproteinVI (GPVI) and purinergic receptor Y12 (P2Y12) receptors is unknown. In silico studies revealed that the indole group of DIM and indole and the hydroxyl group of I3C are responsible for modulating platelet interaction with GPVI and P2Y12 receptors. In silico studies further predicted that DIM more superiorly modulates platelet interaction with GPVI and P2Y12 receptors than I3C. In vitro studies identified that DIM significantly inhibited platelet aggregation induced by adenosine diphosphate (ADP), collagen, thrombin, and arachidonic acid, increasing the thrombin-induced clot retraction size and clot retraction weight. Moreover, in vivo results of ferric chloride (FeCl3) induced carotid artery thrombus generation indicate that DIM significantly reduced the reactive oxygen species (ROS), hydrogen peroxide (H2O2), thromboxane 2 (TXB2), cyclooxygenase 1 (COX-1), prostaglandin E2 (PGE2), thrombus weight, increased the cyclic adenosine monophosphate (cAMP), and extended the time to occlusion (TTO). Furthermore, DIM did not show thrombolytic activity. Therefore, DIM acts as an antiplatelet aggregation and antithrombotic agent. Moreover, DIM is responsible for the antiplatelet aggregation and antithrombotic activity of I3C. Therefore, DIM could be used to treat thrombotic diseases.

Synthesis of DPIE [2-(1,2-Diphenyl-1H-indol-3-yl)ethanamine] Derivatives and Their Regulatory Effects on Pro-Inflammatory Cytokine Production in IL-1β-Stimulated Primary Human Oral Cells.

Interleukin-1 beta (IL-1β) has diverse physiological functions and plays important roles in health and disease. In this report, we focus on its function in the production of pro-inflammatory cytokines, including IL-6 and IL-8, which are implicated in several autoimmune diseases and host defense against infection. IL-1β activity is markedly dependent on the binding affinity toward IL-1 receptors (IL-1Rs). Several studies have been conducted to identify suitable small molecules that can modulate the interactions between 1L-1β and 1L-1R1. Based on our previous report, where DPIE [2-(1,2-Diphenyl-1H-indol-3-yl)ethanamine] exhibited such modulatory activity, three types of DPIE derivatives were synthesized by introducing various substituents at the 1, 2, and 3 positions of the indole group in DPIE. To predict a possible binding pose in complex with IL-1R1, a docking simulation was performed. The effect of the chemicals was determined in human gingival fibroblasts (GFs) following IL-1β induction. The DPIE derivatives affected different aspects of cytokine production. Further, a group of the derivatives enabled synergistic pro-inflammatory cytokine production, while another group caused diminished cytokine production compared to DPIE stimulation. Some groups displayed no significant difference after stimulation. These findings indicate that the modification of the indole site could modulate IL-1β:IL1R1 binding affinity to reduce or enhance pro-inflammatory cytokine production.

Endophytic, Non-endophytic Fungal Alkaloids and its Applications

Alkaloids are a secondary metabolite, which are extracted from a wide – array of organisms include Bacteria, Fungi, Plants and Animals. Here in present review mainly focused on the alkaloids derived from endophytic fungi and non – endophytic fungi. Fungi have provided a great source of spirit for novel drug compounds as fungi derived alkaloids have done major boon to human health and well - being. In the present review listed 35 different group of alkaloids from endophytes. In which 12 different alkaloids are kept under derivatives of Indole group, 4 different alkaloids are kept under Quinoline group, 4 different alkaloids kept under amines and amide group, from non-endophytic alkaloid 27 different group of alkaloids are reported. In which 9 different type of alkaloid are mentioned under indole group of alkaloids, 4 alkaloids are reported under diketopiperazine alkaloids, 4 different alkaloids are mentioned under ergot group of alkaloids, 3 alkaloids under prenylated indole alkaloids, 3 alkaloids are mentioned under pyridine classes. The main applications of these alkaloids are antimicrobial, Antibacterial, Antifungal, Antiviral Activity Antihelmenthic, Anticancerous, Nutrient Pedaling, Photo stimulation, Endophytes in Tissue Culture Antidiabetic Activity, and Immunosuppressive Activity; hence all the alkaloids should be used as medicines in Ayurvedam. The alkaloids derived from different fungi were reviewed and their uses in medical fields were also report.

Indole metabolism by phenol-stimulated activated sludges: Performance, microbial communities and network analysis

Indole and phenol often coexist in the coking wastewater, while the effects of phenol on microbial communities of indole metabolism were less explored. In this study, the microbial interactions within activated sludge microbial communities stimulated by indole (group A) or by indole and phenol (group B) were systematically investigated in sequencing batch reactors (SBRs). The results showed that the removal of indole was increased by adding phenol. By using high-throughput sequencing technology, it was found that α-diversity was reduced in both groups. According to the relative abundance analysis, the indole-degrading genus Comamonas was the core genus in both groups (33.94% and 61.40%). But another indole-degrading genus Pseudomonas was only enriched in group A with 12.22% relative abundance. Meanwhile, common aromatic degrading genus Dyella and Thermomonas were enriched only in group B. It was found that the relative abundance of cytochrome P450 and styrene degradation enzymes were increased in group B by PICRUSt analysis. Based on the phylogenetic molecular ecological networks (pMENs), module hub OTU_1149 (Burkholderia) was only detected in group B, and the positive interactions between the key functional genus Burkholderia and other bacteria were increased. This study provides new insights into our understanding of indole metabolism communities stimulated by phenol, which would provide useful information for practical coking wastewater treatment.

A magnetic porous organic polymer: catalytic application in the synthesis of hybrid pyridines with indole, triazole and sulfonamide moieties.

Herein, the synthesis and characterization of a triazine-based magnetic ionic porous organic polymer are reported. The structure, morphology, and components of the prepared structure have been investigated with several spectroscopic and microscopic techniques such as FT-IR, EDX, elemental mapping, TGA/DTA, SEM, TEM, VSM, and BET analysis. Also, catalytic application of the prepared triazine-based magnetic ionic porous organic polymer was investigated for the synthesis of hybrid pyridine derivatives bearing indole, triazole and sulfonamide groups. Furthermore, the prepared hybrid pyridine systems were characterized by FT-IR, 1H NMR, 13C NMR and mass analysis. A cooperative vinylogous anomeric-based oxidation pathway was suggested for the synthesis of target molecules.

Pharmacophore Modelling and 4D QSAR Analysis of Some Indole Glyoxamide Derivatives as HIV-1 Binding Inhibitors

The main aim of this study is to uncover the main pharmacophoric features of a series of indole glyoxamide derivatives which are known as HIV-1 attachment inhibitors and to estimate the biological activity to develop a 4D-QSAR model by using the EC-GA method. Conformational analysis and quantum mechanical calculations were accomplished by using the Hartree Fock method with the 3-21G basis set. Based on the data produced from the quantum chemical calculations, the electron conformational matrices of congruity (ECMC)s, as the 3D- arrangement of electronic and geometric properties, were generated by the EMRE program. An individual ECMC was formed for each conformer of each indole glyoxamide derivative in the data set. Conformational flexibility was considered for each compound. Totally 1510 ECMCs were produced by EMRE software to be used in the comparison process. By analogizing the ECMCs in a predetermined tolerance value, the subset of common features matching all active compounds but not matching the low activity compounds was determined. The final ECSA was obtained as a set of nine atoms including predominantly hydrogen bond donors, hydrogen bond acceptors and lipophilic units. Key elements are mainly placed in indole nitrogen, carbonyl groups and piperazine ring. In the bioactivity prediction and variable selection, the genetic algorithm and non-linear least square techniques were employed. The obtained models were internally and externally validated by the leave-one-out cross-validation method. The resulting 4D QSAR EC-GA models were compared with the other methods and the best model with the high prediction ability was defined according to R2training=, R2test =0.8 cross-validatedated q2 =0.860, q2ext1 = 0.850 and q2ext1 = 0.850 values. Attained EC-GA model provides insight into the vital interaction between indole glyoxamide derivatives and the target protein. EC-GA models can be utilized as an effective and confidential tool in the design of more potent indole glyoxamide derivatives.

ADC Thresholds in the Discrimination of Indolent and Aggressive Orbital Adnexal Lymphoma

Aim: This study aims to determine whether ADC measurements allow discrimination of indolent (group A) from aggressive orbital lymphoma (group B) and how much ADC value can predict lymphoma subtype. Methods: A retrospective two-armed cohort study including 32 Orbital Adnexal Lymphoma (OAL) lesions evaluated by conventional magnetic resonance image (MRI) and Diffusion Weighted Image (DWI) examination preceding histopathological lesion confirmation. DWI using single-shot echo-planar imaging with b factors of 0,400 and 800 sec/mm2 were performed on 3 Tesla MRI unit. Lymphomas were grouped into indolent or aggressive histopathological subtypes according to the Revised European-American Classification of Lymphoid Neoplasms (REAL). The groups minimum, maximum and percentiles of ADC values of indolent were compared to those of aggressive lymphoma subtype. Multiple receiver operating characteristic curve (ROC) analysis was performed for predicting aggressive OAL. Results: Of the 32 (OAL) cases, 23 (71.9%) were indolent and 9 (28.1%) were aggressive OAL subtypes. In general, ADC values were significantly higher in the indolent compared to the aggressive OL subtypes. (P&lt;0.001). Extra-ocular muscles (P = 0.69) and globe involvement (P = 0.9) were not significant confounders for association of ADC to histological type. The area under curve (AUC) for ADC minimum was 94.4% and for ADC maximum was 81.6%. ADC minimum showed higher sensitivity and specificity than ADC maximum in revealing (OAL) subtypes. Conclusions: ADC measurements are higher in indolent than in aggressive (OAL). ADC minimum has higher sensitivity and specificity than ADC maximum in (OAL) lesions. These concepts confirm and expand the knowledge on (OAL), revealing the importance of ADC minimum in discriminate indolent from aggressive OAL. DWI can be used to characterize (OAL) based on ADC values, having higher sensitivity and specificity to point the (OAL) subtypes.

A benzimidazole scaffold as a promising inhibitor against SARS-CoV-2

The manuscript reports the green-chemical synthesis of a new diindole-substituted benzimidazole compound, B1 through a straightforward route in coupling between indolyl-3-carboxaldehyde and o-phenylenediamine in water medium under the aerobic condition at 75 ºC. The single crystal X-ray structural analysis of B1 suggests that the disubstituted benzimidazole compound crystallizes in a monoclinic system and the indole groups exist in a perpendicular fashion with respect to benzimidazole moiety. The SARS-CoV-2 screening activity has been studied against 1 × 10e4 VeroE6 cells in a dose-dependent manner following Hoechst 33342 and nucleocapsid staining activity with respect to remdesivir. The compound exhibits 92.4% cell viability for 30 h and 35.1% inhibition against VeroE6 cells at non-cytotoxic concentration. Molecular docking studies predict high binding propensities of B1 with the main protease (Mpro) and non-structural (nsp2 and nsp7-nsp8) proteins of SARS-CoV-2 through a number of non-covalent interactions. Molecular dynamics (MD) simulation analysis for 100 ns confirms the formation of stable conformations of B1-docked proteins with significant changes of binding energy, attributing the potential inhibition properties of the synthetic benzimidazole scaffold against SARS-CoV-2. Communicated by Ramaswamy H. Sarma

Indole derivative XCR-5a alleviates LPS-induced inflammation in vitro and in vivo

Context Few studies on anti-inflammatory drugs with indole groups have been published. This is the first study that demonstrates the anti-inflammatory effects of indole derivative XCR-5a in vitro and in vivo. Objective This study aimed to discover more anti-inflammatory drugs with indole groups and investigate their anti-inflammatory mechanisms. Materials and methods First, a series of indole derivatives was synthesized, then screened for XCR-5a, a compound with anti-inflammatory effects. Second, the in vitro production of IL-1β, IL-6, TNF-α, inducible nitric oxide synthase (iNOS), and cyclo-oxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced primary cells of mice pretreated with XCR-5a was determined using qPCR and ELISA. Finally, the effect of XCR-5a on LPS-induced NF-κB signaling activation was determined by Western blotting. An in vivo mouse sepsis model was established. In mouse lung tissue, the production of IL-1β, IL-6, and TNF-α was determined and H&E staining was performed. Results Our findings showed that XCR-5a could suppress the production of LPS-induced IL-1β, IL-6, and TNF-α, as well as mRNA expression of iNOS and COX-2. Pretreatment with XCR-5a inhibited the LPS-induced inflammatory response in septic mice in vivo by decreasing pro-inflammatory cytokines production in serum and reducing immune cell infiltration. Mechanistically, XCR-5a suppressed LPS-induced activation of the NF-κB signaling pathway. Conclusions XCR-5a has anti-inflammatory effects in vitro and in vivo. Therefore, XCR-5a could be a potential drug candidate for the treatment of inflammatory diseases.

Bacterial neurotoxic metabolites in multiple sclerosis cerebrospinal fluid and plasma.

The identification of intestinal dysbiosis in patients with neurological and psychiatric disorders has highlighted the importance of gut-brain communication, and yet the question regarding the identity of the components responsible for this cross-talk remains open. We previously reported that relapsing remitting multiple sclerosis patients treated with dimethyl fumarate have a prominent depletion of the gut microbiota, thereby suggesting that studying the composition of plasma and CSF samples from these patients may help to identify microbially derived metabolites. We used a functional xenogeneic assay consisting of cultured rat neurons exposed to CSF samples collected from multiple sclerosis patients before and after dimethyl fumarate treatment to assess neurotoxicity and then conducted a metabolomic analysis of plasma and CSF samples to identify metabolites with differential abundance. A weighted correlation network analysis allowed us to identify groups of metabolites, present in plasma and CSF samples, whose abundance correlated with the neurotoxic potential of the CSF. This analysis identified the presence of phenol and indole group metabolites of bacterial origin (e.g. p-cresol sulphate, indoxyl sulphate and N-phenylacetylglutamine) as potentially neurotoxic and decreased by treatment. Chronic exposure of cultured neurons to these metabolites impaired their firing rate and induced axonal damage, independent from mitochondrial dysfunction and oxidative stress, thereby identifying a novel pathway of neurotoxicity. Clinical, radiological and cognitive test metrics were also collected in treated patients at follow-up visits. Improved MRI metrics, disability and cognition were only detected in dimethyl fumarate-treated relapsing remitting multiple sclerosis patients. The levels of the identified metabolites of bacterial origin (p-cresol sulphate, indoxyl sulphate and N-phenylacetylglutamine) were inversely correlated to MRI measurements of cortical volume and directly correlated to the levels of neurofilament light chain, an established biomarker of neurodegeneration. Our data suggest that phenol and indole derivatives from the catabolism of tryptophan and phenylalanine are microbially derived metabolites, which may mediate gut-brain communication and induce neurotoxicity in multiple sclerosis.

Green synthesis of silver nanoparticles from papaya seed extracts with alkaloid content for antibacterial application

This research aims to develop a silver nanoparticle (AgNPs) using several plant extracts for antibacterial application. The papaya seed extract has been fractioned by n-hexane, ethyl acetate, water, and ethanol. The n-hexane fraction was the only fraction that succeeded in synthesizing AgNPs. The characterization methods showed AgNPs marked at 430 nm with UV-Vis and 1640 cm-1 with FTIR. SEM observed the aggregation of spherical AgNPs at the 200 nm scale. The particle size of 91.3 nm was measured with PSA that confirmed the nanoscale of the synthesized material. All fractions contained alkaloid compound, and ethyl acetate fraction showed a group of indole with specific wavenumber at 2623 cm-1, 1737 cm-1, and 1237 cm-1 representing N-H, C=O, C-N, respectively. All fractions at every concentration (25%, 50%, 75%, 100%) have been tested and showed the medium effect on bacterial growth inhibition. Among all fractions, the AgNPs n-hexane fraction has the highest bacterial effect, which was indicated by mean values of inhibition zone 7.2 mm against S.aureus, as well as 6.6 mm against E.coli. ANOVA analysis showed that AgNPs n-hexane fraction has a significant inhibition zone compared to other fractions against S.aureus (p=0.002), but not significant to E.coli (p=0.128). The insignificant results on E.coli because of gram-negative bacteria's biophysical characteristics, such as membrane cell wall and flagellin. This research emphasized that AgNPs could be synthesized via a green process of nucleation by using plant extract that effectively inhibits the growth of S.aureus and E.coli. Further studies on the mechanism of the antibacterial effect at the molecular level might be investigated soon.