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Antibiotics are critical in the management of a variety of bacterial infections, however, repeated infections produced by relentless bacteria are obstructing effective infection treatment and it is the most significant and vexing problem at the moment. Medicinal chemists face a difficult problem in developing appropriate lead compounds for various diseases, isatin and its hybrids would be one of them due to its versatility in many medications and its derivatives exhibit an extensive variety of structural and mechanistic properties. This review looks at the isatin hybrids that have probable antibacterial action. The structure-activity relationship (SAR) and the way of producing action are also examined in order to locate the course for the intent and expansion of isatin hybrids by means of increased efficacy, reduced toxicity and good pharmacokinetic profiles. Based on the findings, it can be inferred that 3-hydrazone, imine, spiro, oxindole, guanidino and N-alkyl, aryl, acyl substituted isatin hybrids with electronegative groups on other heterocycles have improved bactericidal activity. Furthermore, the antibacterial activity of isatin is dependent on the binding linkage, such as amide (NHCO), carbonyl (CO) or other hetero atom-containing linkers that have improved antibacterial activity. This review gives an idea and scope for the synthesis of novel isatin-containing heterocyclics with the goal of having potent bactericidal activity.

The West African liana Ancistrocladus abbreviatus is a rich source of structurally most diverse naphthylisoquinoline alkaloids. From its roots, a series of four novel representatives, named ancistrobrevolines A–D (14–17) have now been isolated, displaying an unprecedented heterocyclic ring system, where the usual isoquinoline entity is replaced by a ring-contracted isoindolinone part. Their constitutions were elucidated by 1D and 2D NMR and HR-ESI-MS. The absolute configurations at the chiral axis and at the stereogenic center were assigned by using experimental and computational electronic circular dichroism (ECD) investigations and a ruthenium-mediated oxidative degradation, respectively. For the biosynthetic origin of the isoindolinones from ‘normal’ naphthyltetrahydroisoquinolines, a hypothetic pathway is presented. It involves oxidative decarboxylation steps leading to a ring contraction by a benzilic acid rearrangement. Ancistrobrevolines A (14) and B (15) were found to display moderate cytotoxic effects (up to 72%) against MCF-7 breast and A549 lung cancer cells and to reduce the formation of spheroids (mammospheres) in the breast cancer cell line.

Ancistrobrevinium A (1) is the first N-methylated and non-hydrogenated, and thus cationic naphthylisoquinoline alkaloid. It was discovered in the root bark extract of the phytochemically productive West African liana Ancistrocladus abbreviatus (Ancistrocladaceae). Its constitution was elucidated by HR-ESI-MS and 1D and 2D NMR. Due to the steric hindrance in the proximity of the linkage between the naphthalene and isoquinoline parts, the biaryl axis is rotationally hindered. It thus constitutes a stable element of chirality – the only one in the new alkaloid since, different from most other naphthylisoquinoline alkaloids, it has no stereogenic centers. The axial configuration of 1 was assigned by electronic circular dichroism (ECD) investigations, which gave a positive couplet, indicating a ‘positive chirality’, here corresponding to a P-configuration. Ancistrobrevinium A (1) showed a weak cytotoxic activity against A549 lung cancer cells (IC50 = 50.6 μM).

Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype generally associated with younger women. Due to the lack of suitable drugable targets in TNBC, the microRNAs are considered as a better hope as therapeutic agents for the management of the disease. In this study, we identified differentially expressed miRNAs (DEMs) and associated hub genes in TNBC microarray data (GSE38167, GSE60714, and GSE10833) using bioinformatics tools. The identified miRNAs and genes were validated in the TNBC cell line model (MDA-MB-231) compared with the normal breast cells (MCF-10A) using the qRT-PCR technique. False-positive DEMs were avoided by comparing the DEMs profile of TNBC and triple positive breast cancer (TPBC) cell line model (BT474) compared with the MCF-10A cells data. In addition, we studied the effect of anticancer phytochemicals on the differential expression of miRNAs and genes in MDA-MB-231 cells. Furthermore, target predictions, functional enrichment and KEGG pathway analysis, mutation and copy number alterations, and overall survival analysis of DEMs in TNBC sample was investigated using standard computational tools. The study identifies first time the association of hsa-miR-1250, has-miR-1273, and has-miR-635 with the TNBC. DEMs showed significant association with the Wnt, ErbB, PI3-Akt and cAMP signaling pathways having clinical implications in TNBC tumorigenesis. The DEMs and hub genes (HOXC6 and ACVR2B) showed survival disadvantages in TNBC patients. In summary, the identified miRNAs and hub genes show important implications in TNBC tumorigenesis and patient survival. We recommend further experimental studies on pathophysiological mechanism of the identified miRNAs and hub genes in TNBC.Communicated by Ramaswamy H. Sarma.

The zinc finger and BTB (broad-complex, tramtrack and bric a brac) domain containing protein 7A (ZBTB7A) is a pleiotropic transcription factor that plays an important role in various stages of cell proliferation, differentiation, and other developmental processes. ZBTB7A is a member of the POK family that directly and specifically binds to short DNA recognition sites located near their target genes thereby acting as transcriptional activator or repressor. ZBTB7A overexpression has been associated with tumorigenesis and metastasis in various human cancer types, including breast, prostate, lung, ovarian, and colon cancer. However in some instances downregulation of ZBTB7A results in tumor progression, suggesting its role as a tumor suppressor. ZBTB7A is involved with complicated regulatory networks which include protein-protein and protein-nucleic acid interactions. ZBTB7A involvement in cancer progression and metastasis is perhaps enabled through the regulation of various signaling pathways depending on the type and genetic context of cancer. The association of ZBTB7A with other proteins affects cancer aggressiveness, therapeutic resistance and clinical outcome. This review focuses on the involvement of ZBTB7A in various signaling pathways and its role in cancer progression. We will also review the literature on ZBTB7A and cancer which could be potentially explored for its therapeutic implications.

A colourless hyphomycetous fungus was found on living leaves of Peristrophe bicalyculata in India. A multigene phylogenetic analysis (LSU-RPB2-ITS) of this strain was performed represents no other known lineage with similar morphology in Mycosphaerellaceae, hence the new genus Neocercosporella is proposed with N. peristrophes comb. nov., based on Cercosporella peristrophes (≡ Pseudocercosporella andrographidis), as type species. Phylogenetic examinations and ultrastructure of conidiogenous loci and hila of conidia of both the type materials from N. peristrophes and P. andrographidis confirm identical strains. The conidiogenous loci are conical, having very small rim-like depression on the top encircling a small flat protuberant like structure that make this novel strain differs from other closely related members of the ramularioid complex. Superficially, the colourless nature with thickened and darkened loci and hila make it closer to Cercosporella, but differs in having terminal and intercalary conidiogenous cells and weak catenation in conidia. Phylogenetically, Neocercosporella is distant from the Cercosporella s. str. clade (type species C. virgaureae). The addition of this novel strain, segregated closely related species in Mycosphaerellaceae therefore, three new genera and four new combinations are introduced in this study. New genera are: Neoacervuloseptoria gen. nov. Neocercosporella gen. nov. and Neoramulariopsis gen. nov. New combinations are: Neoacervuloseptoria fraxini comb. nov., Neocercosporella peristrophes comb. nov., Neoramulariopsis catenulata comb. nov. and Neoramulariopsis dolichandrae comb. nov.

Electrocatalytic oxidation (EO) of carcinogenic 4-aminobiphenyl (4-ABP) aromatic amine was performed using Ti-RuO

Androgen deprivation therapy (ADT) is a standard treatment modality for locally advanced, high-risk, and metastatic hormone-sensitive prostate cancer. Long-term ADT treatment likely develops side-effects that include changes in cognition or onset of dementia. However, the molecular understanding of this effect remains elusive. We attempt to establish a link between ADT and changes in cognitive function using patient databases and bioinformatics analyses.Gene expression profiling was performed using RNA sequencing data from Alzheimer patient cohort and compared with the data from advanced-stage prostate cancer patients receiving neoadjuvant antiandrogen therapy. Differentially expressed genes (DEGs) were analyzed using the Ingenuity knowledge database.A total of 1952 DEGs in the Alzheimer patient cohort and 101 DEGs were identified in ADT treated prostate cancer patients. Comparing both data sets provided a subset of 33 commonly expressed genes involving cytokine-cytokine signaling with an over representation of cytokine-cytokine receptor interaction, inflammatory cytokines, signaling by interleukins together with alterations in the circulating lymphocyte repertoire, adaptive immune responses, regulation of cytokine production, and changes in T-cell subsets. Additionally, lipopolysaccharide, tumor necrosis factor, and toll-like receptors were identified as upstream transcriptional regulators of these pathways. The most commonly expressed genes viz. IL-17A, CCL2, IL-10, IL-6, IL-1RN, LIF/LIFR were further validated by quantitative RT-PCR exhibited higher expression in antiandrogen treated neuronal, glial, and androgen-responsive prostate cancer cells, compared to no-androgen antagonist treatment.Our findings suggest that changes in cytokine signaling under the influence of ADT in prostate cancer patients may be linked with cognitive impairment presenting new avenues for diagnostic and therapeutic development in combating brain deficits.

In the present comparative study, the authors studied the antioxidant and anticancer activity of commercially available polyherbal Indian Ayurvedic products namely Divya Sarvakalp Kwath (DSKK), Divya Sanjivani Vati (DSV), Kanchanar Guggulu (KG) and Shakti Drop (SD). Authors also quantified phenolic and flavonoid contents in the samples. Solid powdered samples (DSKK, DSV, and KG) were extracted in methanol and water (1:1) using cold extraction method. Spectrophotometry technique was used to quantify the phytochemicals present in test samples. DSKK showed comparatively higher content of total phenolics (247.65 ± 0.05 μgPGE/g) and flavonoid (34.66 ± 0.19 µgQE/mg). Radical scavenging, metal ion chelation and reducing potential of test products were studied using nitric oxide scavenging, DPPH, metal ion chelation, reducing power ability, and phosphomolybdate in vitro antioxidant assays at different concentration. Dose-dependent antioxidant activity was observed in all the test samples at 100–500 µg or µl/ml concentration. Anticancer efficacy of the test samples were studied in lung (A549), colon (Colo205), and breast cancer (MCF7) cell lines at different concentrations (10–100 µg or µl/ml) using MTT assay. Confocal microscopy was used to reveal the apoptotic induction, mitochondrial membrane integrity disruption and reactive oxygen species production ability of test products in cancer cells. The present study revealed that DSKK possesses comparatively better antioxidant potential and SD has potent anticancer activity against breast cancer cells.

The Melanoma Antigen Gene (MAGE) protein family is a large and highly conserved group of proteins that share a common MAGE homology domain. Interestingly, several MAGE proteins are limited in expression to reproductive tissues but are aberrantly expressed in various types of human malignancies. We have recently demonstrated overexpression of MAGE family member A6 in advance-stage bladder cancer (Cancers 13:23, 5931, 2021). However, the mechanisms involved in MAGE gene overexpression and its coregulators are currently unknown. One hypothesis is that MAGEA6 and androgen receptor (AR) signaling is involved in the etiology of bladder cancer progression. In the present study, we determined the functional relationship between MAGEA6 and AR in bladder cancer. Treatment with DHT, an AR agonist, increased AR and MAGEA6 expression in UMUC3 and J82 bladder cancer cells at the protein and transcript level. On the contrary, exposure of cells to enzalutamide, an antiandrogen, resulted in simultaneous reduction of AR and MAGEA6 more prominently in UMUC3 cells, compared to J82 harboring low MAGEA6 transcript. Dual-sgRNA CRISPR/Cas9 knockout of MAGEA6 in UMUC3 and J82 cells resulted in inhibition of cell proliferation, reduced survival, and migration potential in both cell lines. An induction of S-phase and G0/G1 phase cell cycle arrest was noted in UMUC3 and J82 cells. In silico analysis showed Arg20 and Cys557 amino acid residue of AR interacts with Asp236 and Gln106 amino acid residue of MAGEA6 through hydrogen bonds. Further confirmation of physical interaction between AR and MAGEA6, performed by immunoprecipitation of AR and probed for MAGEA6 and vice versa established interaction of AR-MAGEA6 with each other which was further confirmed by mass spectrometry analysis. In conclusion, these findings confirm the oncogenic role of MAGEA6 and its physical interaction with AR may be involved in bladder cancer progression. Citation Format: Prem Prakash Kushwaha, Shiv Verma, Sanjay Gupta. Melanoma antigen gene A6 and androgen receptor interaction in bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1498.

Aberrant activation of Notch signaling pathway plays an important role in breast cancer development, progression, and stem cell renewal. Activation of Notch signaling is triggered by the interaction of Notch receptors with different ligands expressed on neighboring cells that bind and induce a second cleavage by a membrane-tethered metalloprotease. The remaining membrane-bound fragment is cleaved by γ-secretase (GS) releasing the Notch Intracellular Domain (NICD), which translocate to the nucleus to activate the expression of Notch target genes. Current indirect approaches to inhibit Notch signaling are based on agents that bind to GS substrates. In the search of novel Notch signaling inhibitor(s), we screened a number of plant flavonoids for their binding potential to GS substrate. Our in-silico study identified kurarinone (KU), a lavandulyl flavanone, having ability to bind to GS complex. The KU-GS complex was structurally and energetically stable during the molecular dynamics simulation period. Interestingly, dose and time dependent toxicity of KU was observed in T47D and MDA-MB-231 breast cancer cells at 1-25µM concentration. KU treatment of cells led to inhibition in cyclin D1 expression, arrest of cells in the G1 phase of the cell cycle and subsequently undergoes apoptosis. KU-mediated apoptosis was a result of altered mitochondria membrane potential and increased ROS production. In dual-luciferase Notch promoter assay, KU inhibited GS-mediated NICD production in transfected HEK293 cells. Furthermore, KU treatment decreased the mammosphere formation potential of MCF-7 cells through altered gene expression involved in self-renewal and stemness. KU treated MDA-MB-231 cells and MCF-7 derived mammosphere showed downregulation of Notch signaling through alteration in the expression of downstream genes such as Hey1, Hes1, and E-cadherin at both transcript and protein levels. Taken together, the present study identified KU as a novel natural Notch signaling inhibitor that could provide a novel and safer approach for the treatment of breast cancer through reduction in stemness and self-renewal properties. Citation Format: Prem Prakash Kushwaha, Mohd Shuaib, Kumari Sunita Prajapati, Atul Kumar Singh, Mahesh Kulharia, Shashank Kumar, Sanjay Gupta. Kurarinone, a natural notch signaling inhibitor and modulator of breast cancer stemness. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4955.

Podosphaera thermopsidicola, a new sexual morph form of powdery mildew was discovered on living leaves of Thermopsis barbata Benth. (Fabaceae). It is described, illustrated and compared with other Podosphaera species reported on Fabaceae. The phylogeny of this species has been inferred from partial nuclear ribosomal 28S large subunit (LSU) and internal transcribed spacer (ITS) rDNA sequence data. On the basis of LSU, P. thermopsidicola represents characteristic feature of Podosphaera s. str. Phylogenetically, P. thermopsidicola is closer to P. erigerontis-canadensis but differs in having larger chasmothecia, longer appendages, thick-walled asci, smaller oculi and smaller ascospores.

ZBTB7A is a member of the POK family of transcription factors that possesses a POZ-domain at the N-terminus and Krüppel-like zinc-finger at the c-terminus. ZBTB7A was initially isolated as a protein that binds to the inducer of the short transcript of HIV-1 virus TAT gene promoter. The protein forms a homodimer through protein-protein interaction via the N-terminus POZ-domains. ZBTB7A typically binds to the DNA elements through its zinc-finger domains and represses transcription both by modification of the chromatin organization and through the direct recruitment of transcription factors to gene regulatory regions. ZBTB7A is involved in several fundamental biological processes including cell proliferation, differentiation, and development. It also participates in hematopoiesis, adipogenesis, chondrogenesis, cellular metabolism and alternative splicing of BCLXL, DNA repair, development of oligodendrocytes, osteoclast and unfolded protein response. Aberrant ZBTB7A expression promotes oncogenic transformation and tumor progression, but also maintains a tumor suppressive role depending on the type and genetic context of cancer. In this comprehensive review we provide information about the structure, function, targets, and regulators of ZBTB7A and its role as an oncogenic driver and transcriptional repressor in various human diseases.

Ortho-phenylenediamine (OPD) and Indole are nitrogenous organic compounds. Ortho-phenylenediamine has been reported to be an endocrine disrupting chemical and is genotoxic in nature, whereas, Indole is mutagenic and carcinogenic. OPD and Indole both all together are present in effluents of several industries, and their simultaneous (binary in the present study) adsorption equilibrium data are required in designing the adsorption system/reactor for separation. Therefore, in the present work, simultaneous adsorption study for adsorption of OPD and Indole from their binary solution, on to low cost commercial grade activated carbon was conducted. Adsorption experiments were performed at 288–318 K, and simultaneous equilibrium adsorption data (binary data in the present study) were collected. Further, various multicomponent competitive isotherms [Langmuir (extended), Freundlich (extended), Sheindorf–Rebuhn–Sheintuch and competitive Redlich–Peterson (modified)] were used to validate the experimental equilibrium isotherm data, and parameters of various isotherms were calculated. Moreover, synergistic/antagonistic effects were also evaluated. Freundlich (extended) and Sheindorf–Rebuhn–Sheintuch isotherm models best represented the experimental data.

Natural deep eutectic solvents (NADESs) are designer green solvents which share many properties with ionic liquids. The uncommon intermolecular adjustment in a NADES matrix shows exceptional solubilizing and stabilizing properties. These properties make them suitable to be used as an entrainer for extractive distillation. The present work investigates the synthesis of choline chloride-based NADES and its viability as an entrainer for separation of acetonitrile (ACN) + water mixture by extractive distillation. A NADES was prepared by employing two natural and biodegradable compounds, dl-malic acid and choline chloride in a 1:1 molar ratio (MC1:1). The vapor–liquid equilibria at isobaric condition were measured for pseudo-binary mixtures (water + MC1:1 and ACN + MC1:1) using an improved Othmer recirculation still at 101.3 kPa. Other than these, the vapor–liquid equilibrium data for ACN + water + MC1:1 pseudo-ternary mixture were also measured at different NADES concentrations. From the results, MC1:1 could ...