One-pot synthesis, NMR, quantum chemical approach, molecular docking studies, drug-likeness and in-silico ADMET prediction of novel 1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-(furan-2-yl)-4,5-diphenyl-1H-imidazole derivatives.

A novel drug to treat SARS-CoV-2 infections and hydroxyl chloroquine analogue, 1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-(furan-2-yl)-4,5-diphenyl-1H-imidazole (DDFDI) compound has been synthesized in one pot reaction. The novel compound DDFDI had been characterized by FT-IR, 1H-NMR and 13C-NMR spectral techniques. The geometrical structure was optimized by density functional theory (DFT) method at B3LYP/6-31G (d, p) as the basis set. The smaller energy value provides the higher reactivity of DDFDI compound than hydroxyl chloroquine and was corrected by high electrophilic and low nucleophilic reactions. The stability and charge delocalization of the molecule were also considered by natural bond orbital (NBO) analysis. The HOMO-LUMO energies describe the charge transfer which takes place within the molecule. Molecular electrostatic potential has also been analysed. Drug likeness and oral activity have been carried out based on Lipinski's rule of five. Molecular docking studies are implemented to analyse the binding energy of the DDFDI compound against Covid-19/6W41, COVID-19/6WCF, COVID-19/6Y84 and COVID-19/6W4B receptors and found to be considered as a better antiviral agents.

Synthesis, crystal structure, Hirshfeld surface analysis, DFT, molecular docking and molecular dynamic simulation studies of (E)-2,6-bis(4-chlorophenyl)-3-methyl-4-(2-(2,4,6-trichlorophenyl)hydrazono)piperidine derivatives.

A novel drug to treat SARS-CoV-2 infections and hydroxyl chloroquine analogue, (E)-2,6-bis(4-chlorophenyl)-3-methyl-4-(2-(2,4,6-trichlorophenyl)hydrazono)piperidine (BCMTP) compound has been synthesized in one pot reaction. The novel compound BCMTP has been characterized by FT-IR, 1H-NMR, 13C-NMR and single-crystal X-ray diffraction patterns. Crystal packing is stabilized by C8-H8A•••Cl10i, C41-H41•••Cl1ii and N1-H1A•••Cl6iii intermolecular hydrogen bonds. From the geometrical parameters, it is observed that the piperidine ring adopts chair conformation. Hirshfeld surface analysis was carried out to quantify the interactions and an interaction energy analysis was done to study the interactions between pairs of molecules. The geometrical structure was optimized by density functional theory (DFT) method at B3LYP/6-31G (d, p) as the basic set. The smaller binding energy value provides the higher reactivity of BCMTP compound than hydroxyl chloroquine and was corrected by high electrophilic and low nucleophilic reactions. The stability and charge delocalization of the molecule were also considered by natural bond orbital (NBO) analysis. The HOMO-LUMO energies describe the charge transfer which takes place within the molecule. Molecular electrostatic potential has also been analysed. Molecular docking studies are implemented to analyse the binding energy of the BCMTP compound against standard drugs such as the crystal structure of ADP ribose phosphatase of NSP3 from SARS-CoV-2 in complex with MES and SARS-CoV-2 main protease with an unliganded active site (2019-nCoV, corona virus disease 2019, COVID-19) and found to be considered having better antiviral agents. Molecular dynamics simulation was performed for COVID-19 main protease (Mpro: 6WCF/6Y84) to understand the elements governing the inhibitory effect and the stability of interaction under dynamic conditions.

Bitter melon protects against ER stress in LS174T colonic epithelial cells.

BACKGROUND: Bitter Melon (BM) has been used as a functional food in traditional Chinese and Indian medicine for many generations and has gained a great deal of attention due to its apparent benefits in moderating some of the pathogenic processes in a variety of inflammatory conditions. BM extract (BME) has been shown to possess strong anti-oxidant properties. In addition, it can ameliorate oxidative stress and potentially ER stress. There is increasing evidence that oxidative and ER stress are major contributors for intestinal secretory cell dysfunction which leads to local inflammation and disease pathogenesis that are hallmarks of inflammatory bowel diseases (IBD). Hence, the search for potential therapeutics against ER stress and oxidative stress in intestinal epithelial secretory cells may provide valuable resources for the management of IBD. The aim of the present study was to investigate the effects of BME in ameliorating ER stress in colonic epithelial cells. METHODS: Human colonic adenocarcinoma LS174T cells were used for the assessment of BME effects on colonic epithelial cells in vitro. Cell viability was assessed using trypan blue exclusion and the effect of BME in ameliorating tunicamycin (TM)-induced ER stress was determined by analysing the mRNA expression of the common ER stress markers; ATF6, XBP1, GRP78, CHOP and PERK by quantitative RT-PCR and GRP78 and CHOP by western blot. RESULTS: In the absence of ER stress, BME exhibited no cell toxicity up to 2.0% w/v and no significant effect on the basal mRNA expression of ER stress markers in LS174T cells. In contrast, pre-treatment of LS174T cells with BME followed by induction of ER stress resulted in a significant decrease in mRNA expression of ATF6, XBP1, GRP78, CHOP and PERK and protein expression of GRP78 and CHOP. Co-treatment during induction of ER stress and post- treatment following induction of ER Stress in LS174T cells resulted in a lower but still significant reduction in mRNA expression levels of most ER stress markers. CONCLUSIONS: This is one of the first studies demonstrating the efficacy of BME in reducing expression of ER stress markers in colonic epithelial cells suggesting the potential of BME as a dietary intervention in ameliorating ER stress and oxidation in IBD. Interestingly, while the most significant effect was seen with pre-treatment of cells with BME there was a reduced but still significant effect when co-treated or even post-treated. This suggests that BME may even be effective in modulating ER stress in the face of an existing cell stress environment.

Synthesis, characterization, molecular modeling, binding energies of ß-cyclodextrin-inclusion complexes of quercetin: Modification of photo physical behavior upon ß-CD complexation.

We prepared a naturally occurring flavanoid namely quercetin from tea leaves and analyzed by Absorption, Emission, FT-IR, 1H, 13C nmr spectra and ESI-MS analysis. The inclusion behavior of quercetin in cyclodextrins like α-, ß-, γ-, per-6-ABCD and mono-6-ABCD cavities were supported such as UV-vis., Emission, FT-IR and ICD spectra and energy minimization studies. From the absorption and emission results, the type of complexes formed were found to depend on stoichiometry of Host:Guest. FT-IR data of CD complexes of quercetin supported inclusion complex formation of the substrate with α-, ß- and γ-CDs. The inclusion of host-guest complexation of quercetin with α-, ß-, γ-CDs, per-6-ABCD and mono-6-ABCDs provides very valuable information about the CD:quercetin complexes, the study also shows that ß-CD complexation improves water solubility, chemical stability and bioavailability of quercetin. Besides, phase solubility studies also supported the formation of 1:1 drug-CD soluble complexes. All these spectral results provide insight into the binding behavior of substrate into CD cavity in the order per-6-ABCD > Mono-6-ABCD > γ-CD > ß-CD > α-CD. The proposed model also finds strong support from the fact with excess CD this exciton coupling disappears indicates the formation of only 1:1 complex.

Polysaccharide-fecal microbiota-based colon-targeted self-nanoemulsifying drug delivery system of curcumin for treating polycystic ovarian syndrome.

The gut microbiome is involved in the pathogenesis of many diseases including polycystic ovarian syndrome (PCOS). Modulating the gut microbiome can lead to eubiosis and treatment of various metabolic conditions. However, there is no proper study assessing the delivery of microbial technology for the treatment of such conditions. The present study involves the development of guar gum-pectin-based solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing curcumin (CCM) and fecal microbiota extract (FME) for the treatment of PCOS. The optimized S-SNEDDS containing FME and CCM was prepared by dissolving CCM (25 mg) in an isotropic mixture consisting of Labrafil M 1944 CS, Transcutol P, and Tween-80 and solidified using lactose monohydrate, aerosil-200, guar gum, and pectin (colon-targeted CCM solid self-nanoemulsifying drug delivery system [CCM-CT-S-SNEDDS]). Pharmacokinetic and pharmacodynamic evaluation was carried out on letrozole-induced female Wistar rats. The results of pharmacokinetic studies indicated about 13.11 and 23.48-fold increase in AUC of CCM-loaded colon-targeted S-SNEDDS without FME (CCM-CT-S-SNEDDS (WFME)) and CCM-loaded colon-targeted S-SNEDDS with FME [(CCM-CT-S-SNEDDS (FME)) as compared to unprocessed CCM. The pharmacodynamic study indicated excellent recovery/reversal in the rats treated with CCM-CT-S-SNEDDS low and high dose containing FME (group 13 and group 14) in a dose-dependent manner. The developed formulation showcasing its improved bioavailability, targeted action, and therapeutic activity in ameliorating PCOS can be utilized as an adjuvant therapy for developing a dosage form, scale-up, and technology transfer.

Exposure of colonic epithelial cells to oxidative and endoplasmic reticulum stress causes rapid potassium efflux and calcium influx.

Endoplasmic reticulum (ER) stress and oxidative stress have recently been linked to the pathogenesis of inflammatory bowel diseases. Under physiological conditions, intestinal epithelial cells are exposed to ER and oxidative stress affecting the cellular ionic homeostasis. However, these altered ion flux 'signatures' during these stress conditions are poorly characterized. We investigated the kinetics of K(+) , Ca(2+) and H(+) ion fluxes during ER and oxidative stress in a colonic epithelial cell line LS174T using a non-invasive microelectrode ion flux estimation technique. ER and oxidative stress were induced by cell exposure to tunicamycin (TM) and copper ascorbate (CuAsc), respectively, from 1 to 24 h. Dramatic K(+) efflux was observed following acute ER stress with peak K(+) efflux being -30·6 and -138·7 nmolm(-2) s(-1) for 10 and 50 µg ml(-1) , respectively (p < 0·01). TM-dependent Ca(2+) uptake was more prolonged with peak values of 0·85 and 2·68 nmol m(-2) s(-1) for 10 and 50 µg ml(-1) TM, respectively (p < 0·02). Ion homeostasis was also affected by the duration of ER stress. Increased duration of TM treatment from 0 to 18 h led to increases in both K(+) efflux and Ca(2+) uptake. While K(+) changes were significantly higher at each time point tested, Ca(2+) uptake was significantly higher only after prolonged treatment (18 h). CuAsc also led to an increased K(+) efflux and Ca(2+) uptake. Functional assays to investigate the effect of inhibiting K(+) efflux with tetraethylammonium resulted in increased cell viability. We conclude that ER/oxidative stress in colonic epithelial cells cause dramatic K(+) , Ca(2+) and H(+) ion flux changes, which may predispose this lineage to poor stress recovery reminiscent of that seen in inflammatory bowel diseases.

Induction of Dectin-1 and asthma-associated signal transduction pathways in RAW 264.7 cells by a triple-helical (1, 3)-ß-D glucan, curdlan.

People living in damp buildings are typically exposed to spore and mycelial fragments of the fungi that grow on damp building materials. There is experimental evidence that this exposure to triple-helical (1, 3)-ß-D glucan and low molecular weight toxins may be associated with non-atopic asthma observed in damp and moldy buildings. However, the mechanisms underlying this response are only partially resolved. Using the pure (1, 3)-ß-D glucan, curdlan, and the murine macrophage cell line, RAW 264.7, there were two objectives of this study. The first was to determine whether signal transduction pathways activating asthma-associated cell signaling pathways were stimulated using mouse transduction Pathway Finder(®) arrays and quantitative real-time (QRT) PCR. The second objective was to evaluate the dose and temporal responses associated with transcriptional changes in asthma-associated cytokines, the signal transduction receptor gene Dectin-1, and various transcription factor genes related to the induction of asthma using customized RT-PCR-based arrays. Compared to controls, the 10(-7) M curdlan treatment induced significant changes in gene transcription predominately in the NFkB, TGF-ß, p53, JAK/STAT, P13/AKT, phospholipase C, and stress signaling pathways. The 10(-8) M curdlan treatment mainly induced NFkB and TGF-ß pathways. Compared to controls, curdlan exposures also induced significant dose- and time-dependent changes in the gene translations. We found that that curdlan as a non-allergenic potentiator modulates a network of transduction signaling pathways not only associated with TH-1, TH-2, and TH-3 cell responses including asthma potentiation, but a variety of other cell responses in RAW 264.7 cells. These results help provide mechanistic basis for some of the phenotypic changes associated with asthma that have been observed in in vitro, in vivo, and human studies and open up a hypothesis-building process that could explain the rise of non-atopic asthma associated with fungi.

Synbiotics as Supplemental Therapy for the Alleviation of Chemotherapy-Associated Symptoms in Patients with Solid Tumours.

Chemotherapy is still the first line of treatment for most cancer patients. Patients receiving chemotherapy are generally prone to infections, which result in complications, such as sepsis, mucositis, colitis, and diarrhoea. Several nutritional approaches have been trialled to counter the chemotherapy-associated side effects in cancer patients, but none have yet been approved for routine clinical use. One of the approaches to reduce or avoid chemotherapy-associated complications is to restore the gut microbiota. Gut microbiota is essential for the healthy functioning of the immune system, metabolism, and the regulation of other molecular responses in the body. Chemotherapy erodes the mucosal layer of the gastrointestinal tract and results in the loss of gut microbiota. One of the ways to restore the gut microbiota is through the use of probiotics. Probiotics are the 'good' bacteria that may provide health benefits if consumed in appropriate amounts. Some studies have highlighted that the consumption of probiotics in combination with prebiotics, known as synbiotics, may provide better health benefits when compared to probiotics alone. This review discusses the different nutritional approaches that have been studied in an attempt to combat chemotherapy-associated side effects in cancer patients with a particular focus on the use of pre-, pro- and synbiotics.

Gut Dysbiosis and Diabetic Foot Ulcer: Role of Probiotics.

Diabetic foot ulcer (DFU) is a multifactorial disease and one of the complications of diabetes. The global burden of DFU in the health sector is increasing at a tremendous rate due to its cost management related to hospitalization, medical costs and foot amputation. Hence, to manage DFU/DWs, various attempts have been made, including treating wounds systematically/topically using synthetic drugs, herbal drugs, or tissue engineering based surgical dressings. However, less attention has been paid to the intrinsic factors that are also the leading cause of diabetes mellitus (DM) and its complications. One such factor is gut dysbiosis, which is one of the major causes of enhancing the counts of Gram-negative bacteria. These bacteria produce lipopolysaccharides, which are a major contributing factor toward insulin resistance and inflammation due to the generation of oxidative stress and immunopathy. These all lead to DM and DFU. Probiotics are the commercial form of beneficial gut microbes that are taken as nutraceuticals by people of all ages to improve gut immunity and prevent gut dysbiosis. However, the role of probiotics has been less explored in the management of DFU. Hence, the therapeutic potential of probiotics in managing DFU is fully described in the current review. This report covers the linkage between gut dysbiosis and DFU, sources of probiotics, the mechanisms of probiotics in DW healing, and the impact of probiotic supplementation in treating DFU. In addition, techniques for the stabilization of probiotics, market status, and patents related to probiotics have been also covered. The relevant data were gathered from PubMed, Scopus, Taylor and Francis, Science Direct, and Google Scholar. Our systematic review discusses the utilization of probiotic supplementation as a nutraceutical for the management of DFU.

Biosimilars in Oncology: Latest Trends and Regulatory Status.

Biologic-based medicines are used to treat a variety of diseases and account for around one-quarter of the worldwide pharmaceutical market. The use of biologic medications among cancer patients has resulted in substantial advancements in cancer treatment and supportive care. Biosimilar medications (or biosimilars) are very similar to the reference biologic drugs, although they are not identical. As patent protection for some of the most extensively used biologics begins to expire, biosimilars have the potential to enhance access and provide lower-cost options for cancer treatment. Initially, regulatory guidelines were set up in Europe in 2003, and the first biosimilar was approved in 2006 in Europe. Many countries, including the United States of America (USA), Canada, and Japan, have adopted Europe's worldwide regulatory framework. The use of numerous biosimilars in the treatment and supportive care of cancer has been approved and, indeed, the count is set to climb in the future around the world. However, there are many challenges associated with biosimilars, such as cost, immunogenicity, lack of awareness, extrapolation of indications, and interchangeability. The purpose of this review is to provide an insight into biosimilars, which include various options available for oncology, and the associated adverse events. We compare the regulatory guidelines for biosimilars across the world, and also present the latest trends and challenges in medical oncology both now and in the future, which will assist healthcare professionals, payers, and patients in making informed decisions, increasing the acceptance of biosimilars in clinical practice, increasing accessibility, and speeding up the health and economic benefits associated with biosimilars.

Intestinal secretory cell ER stress and inflammation.

Data from animal models and human inflammatory bowel diseases have implicated the ER (endoplasmic reticulum) stress pathway in intestinal inflammation. We have characterized the development of inflammation in Winnie mice in which ER stress arises due to a single missense mutation in the MUC2 mucin produced by intestinal goblet cells. This model has allowed us to explore the genesis of inflammation ensuing from a single gene polymorphism affecting secretory cells. In these mice, a proportion of MUC2 misfolds during biosynthesis, leading to ER stress and activation of the unfolded protein response. Winnie mice develop spontaneous complex progressive inflammation that is most severe in the distal colon. Inflammation involves TH1, TH2 and TH17 T-cells, with a progressive development of a TH17-dominated response, but also involves innate immunity, in a pattern not dissimilar to human colitis. Experimental inhibition of tolerance in this model severely exacerbates colitis, demonstrating active effective suppression of inflammation. Even though the misfolding of MUC2 is a consequence of an inherited mutation, as inflammation develops, the molecular markers of ER stress increase further and goblet cell pathology becomes worse, suggesting that inflammation itself exacerbates ER stress.

An Appraisal of the Current Scenario in Vaccine Research for COVID-19.

The recent coronavirus disease 2019 (COVID-19) outbreak has drawn global attention, affecting millions, disrupting economies and healthcare modalities. With its high infection rate, COVID-19 has caused a colossal health crisis worldwide. While information on the comprehensive nature of this infectious agent, SARS-CoV-2, still remains obscure, ongoing genomic studies have been successful in identifying its genomic sequence and the presenting antigen. These may serve as promising, potential therapeutic targets in the effective management of COVID-19. In an attempt to establish herd immunity, massive efforts have been directed and driven toward developing vaccines against the SARS-CoV-2 pathogen. This review, in this direction, is aimed at providing the current scenario and future perspectives in the development of vaccines against SARS-CoV-2.

ER stress and the unfolded protein response in intestinal inflammation.

Endoplasmic reticulum (ER) stress is a phenomenon that occurs when excessive protein misfolding occurs during biosynthesis. ER stress triggers a series of signaling and transcriptional events known as the unfolded protein response (UPR). The UPR attempts to restore homeostasis in the ER but if unsuccessful can trigger apoptosis in the stressed cells and local inflammation. Intestinal secretory cells are susceptible to ER stress because they produce large amounts of complex proteins for secretion, most of which are involved in mucosal defense. This review focuses on ER stress in intestinal secretory cells and describes how increased protein misfolding could occur in these cells, the process of degradation of misfolded proteins, the major molecular elements of the UPR pathway, and links between the UPR and inflammation. Evidence is reviewed from mouse models and human inflammatory bowel diseases that ties ER stress and activation of the UPR with intestinal inflammation, and possible therapeutic approaches to ameliorate ER stress are discussed.

STAT4 isoforms differentially regulate Th1 cytokine production and the severity of inflammatory bowel disease.

STAT4, a critical regulator of inflammation in vivo, can be expressed as two alternative splice forms, a full-length STAT4alpha, and a STAT4beta isoform lacking a C-terminal transactivation domain. Each isoform is sufficient to program Th1 development through both common and distinct subsets of target genes. However, the ability of these isoforms to mediate inflammation in vivo has not been examined. Using a model of colitis that develops following transfer of CD4(+) CD45RB(high) T cells expressing either the STAT4alpha or STAT4beta isoform into SCID mice, we determined that although both isoforms mediate inflammation and weight loss, STAT4beta promotes greater colonic inflammation and tissue destruction. This correlates with STAT4 isoform-dependent expression of TNF-alpha and GM-CSF in vitro and in vivo, but not Th1 expression of IFN-gamma or Th17 expression of IL-17, which were similar in STAT4alpha- and STAT4beta-expressing T cells. Thus, higher expression of a subset of inflammatory cytokines from STAT4beta-expressing T cells correlates with the ability of STAT4beta-expressing T cells to mediate more severe inflammatory disease.

Identification of Key Pro-Survival Proteins in Isolated Colonic Goblet Cells of Winnie, a Murine Model of Spontaneous Colitis.

BACKGROUND: Accumulating evidence suggests that the goblet cell-derived mucin-2 (Muc2) is a major component of the immune system and that perturbations in Muc2 lead to an ulcerative colitis-like phenotype. The animal model Winnie carries a missense mutation in Muc2 that causes Muc2 misfolding, accumulation in goblet cells, and ER stress. Excessive ER stress is a hallmark of many diseases, including ulcerative colitis, cancer, diabetes and Parkinson's disease. However, rather than committing to cell death, which is the typical outcome of unresolved ER stress, Winnie goblet cells are characterized by hyperproliferation, suggesting additional regulation of this cellular stress response. METHODS: To elucidate the molecular mechanisms underlying ulcerative colitis in the Winnie model, we isolated goblet cells from Winnie and wild-type mice and used label-free quantitative proteomics and bioinformatics to understand the functional consequences of Muc2 misfolding and accumulation. RESULTS: A large number of changes were identified that highlight a dramatic reprogramming of energy production, including enhanced utilization of butyrate, a key energy source of colonic cells. A major finding was the marked upregulation of the coiled-coil-helix-coiled-coil-helix domain proteins Chchd2, Chchd3, and Chchd6. In particular, we identified and confirmed the upregulation and nuclear translocation of Chchd2, a protein known to inhibit oxidative stress induced apoptosis. CONCLUSIONS: This study is the first to apply proteome-level analysis to the preclinical Winnie model of ulcerative colitis. Identification of proteins and pathways affected in isolated Winnie goblet cells provides evidence for novel adaptive mechanisms underlying cell survival under conditions of chronic ER stress.

Anti-Heartburn Effects of Sugar Cane Flour: A Double-Blind, Randomized, Placebo-Controlled Study.

Gastroesophageal reflux disease (GERD) affects approximately 20% of Australians. Patients suffer a burning sensation known as heartburn due to the movement of acidic stomach content into the esophagus. There is anecdotal evidence of the effectiveness of prebiotic sugarcane flour in controlling symptoms of GERD. This pilot study aimed to investigate the effectiveness of a prebiotic sugarcane flour in alleviating symptoms in medically-diagnosed GERD patients. This pilot study was a single center, double-blinded, placebo-controlled randomized trial conducted on 43 eligible participants. The intervention group (n = 22) were randomized to receive 3 g of sugarcane flour per day, and the control group (n = 21) received 3 g of cellulose placebo per day. Symptoms of gastroesophageal reflux disease were assessed before and after three weeks treatment using the validated Gastroesophageal Reflux Disease-Health Related Quality of Life questionnaire (GERD-HRQL). After three weeks there were significant differences in symptoms for heartburn, regurgitation, and total symptoms scores (p < 0.05) between the sugarcane flour and placebo. Mean GERD-HRQL scores increased in the placebo group for regurgitation (mean increase 1.7; 95% CI 0.23 to 3.2; p = 0.015) and total symptom scores (2.9; 95% CI 0.26 to 5.7; p = 0.033). In contrast, there were significant reductions in heartburn (mean decrease -2.2; 95% CI -4.2 to -0.14; p = 0.037) and total symptom scores (-3.7; 95% CI -7.2 to -0.11; p = 0.044) in the intervention group. This pilot study has shown significant positive effects of sugarcane flour in the reduction of GERD symptoms, and a larger randomized controlled trial is warranted.

Streptococcus Thermophilus UASt-09 Upregulates Goblet Cell Activity in Colonic Epithelial Cells to a Greater Degree than other Probiotic Strains.

Probiotics have been widely used in maintaining gastrointestinal health, despite their actual mechanism remaining obscure. There are several hypotheses behind the beneficial effects of probiotics including the regulation of intestinal barrier function and improvement in immune responses in the gastrointestinal system. Multiple probiotics have been introduced in the market as effective dietary supplements in improving gastrointestinal integrity, but there are no or few studies that demonstrate their underlying mechanism. In the current study, we investigated and compared the efficacy of four probiotics (based on different bacterial species) in refining gastrointestinal health by improving mucus biosynthesis and intestinal immune response under in-vitro conditions. By analyzing the gene expression of mucus biosynthesis and intestinal immune response markers, we found that probiotic Streptococcus thermophilus UASt-09 showed promising potential in refining mucosal barrier and gastrointestinal health in human colonic epithelial cells, as compared to other commercial probiotics.

Synthesis, characterization, computational calculation and biological studies of some 2,6-diaryl-1-(prop-2-yn-1-yl)piperidin-4-one oxime derivatives.

A new series of 2,6-diaryl-1-(prop-2-yn-1-yl)piperidin-4-one oximes (17-24) were designed and synthesized from 2,6-diarylpiperidin-4-one oximes (9-16) with propargyl bromide. Unambiguous structural elucidation has been carried out by investigating IR, NMR ((1)H, (13)C, (1)H-(1)H COSY and HSQC), mass spectral techniques and theoretical (DFT) calculations. Further, crystal structure of compound 17 was evaluated by single crystal X-ray diffraction analysis. Single crystal X-ray structural analysis of compound 17 evidenced that the configuration about CN double bond is syn to C-5 carbon (E-form). The existence of chair conformation was further confirmed by theoretical DFT calculation. All the synthesized compounds were screened for in vitro antimicrobial activity against a panel of selected bacterial and fungal strains using Ciprofloxacin and Ketoconazole as standards. The minimum inhibition concentration (MIC) results revealed that most of the 2,6-diaryl-1-(prop-2-yn-1-yl)piperidin-4-one oximes (17, 19, 20 and 23) exhibited better activity against the selected bacterial and fungal strains.