Recent Discoveries of Nitrogen-Containing Heterocyclic Compounds as InhA Inhibitors against : An Overview.

It is a formidable challenge to treat tuberculosis as there are increasing cases of multidrugresistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) cases. Moreover, the emergence of totally drug-resistant tuberculosis (TDR-TB) makes it vital and imperative to develop a new generation of anti-tubercular drugs to have control over resistance. The nitrogencontaining heterocyclic class of compounds is being studied extensively to ascertain their anti-TB potentials.

Hypoglycemic and Hypolipidemic Swords: Synthesis and Biological Assessment of 5-benzylidene-2,4-thiazolidinediones.

Thiazolidinedione (TZD), being a privileged scaffold, has been known as a significant structural moiety of antidiabetic drugs. TZD has been known to improve glycaemic control in type 2 diabetes mellitus (T2DM) by increasing insulin sensitivity in the body. A novel series of 5-benzylidene 2,4-thiazolidinedione derivatives were designed, synthesized (V1-V28), and structurally confirmed by different spectroscopic techniques such as FTIR, H NMR, C NMR, and Mass spectrometry.

Essential Oil Nanoemulsion as Eco-Friendly and Safe Preservative: Bioefficacy Against Microbial Food Deterioration and Toxin Secretion, Mode of Action, and Future Opportunities.

Microbes are the biggest shareholder for the quantitative and qualitative deterioration of food commodities at different stages of production, transportation, and storage, along with the secretion of toxic secondary metabolites. Indiscriminate application of synthetic preservatives may develop resistance in microbial strains and associated complications in human health with broad-spectrum environmental non-sustainability. The application of essential oils (EOs) as a natural antimicrobial and their efficacy for the preservation of foods has been of present interest and growing consumer demand in the current generation.

Mechanistic Insights into Binding of Ligands with Thiazolidinedione Warhead to Human Histone Deacetylase 4.

Recently, we have reported that non-hydroxamate thiazolidinedione (TZD) analogs are capable of inhibiting human deacetylase 4 (HDAC4). This study aims at the dissection of the molecular determinants and kinetics of the molecular recognition of TZD ligands by HDAC4. For this purpose, a structure activity relationship analysis of 225 analogs was combined with a comprehensive study of the enzyme and binding kinetics of a variety of HDAC4 mutant variants.

Multi-target weapons: diaryl-pyrazoline thiazolidinediones simultaneously targeting VEGFR-2 and HDAC cancer hallmarks.

In anticancer drug discovery, multi-targeting compounds have been beneficial due to their advantages over single-targeting compounds. For instance, VEGFR-2 has a crucial role in angiogenesis and cancer management, whereas HDACs are well-known regulators of epigenetics and have been known to contribute significantly to angiogenesis and carcinogenesis. Herein, we have reported nineteen novel VEGFR-2 and HDAC dual-targeting analogs containing diaryl-pyrazoline thiazolidinediones and their and biological evaluation.

Development and investigation of thiazolidinedione and pyrazoline compounds as antiangiogenic weapons targeting VEGFR-2.

Angiogenesis deregulation is often linked to cancer and is thus an essential target. Twenty-nine compounds were developed as VEGFR-2 inhibitors. Compounds were evaluated to determine their antiangiogenic activity.

Double-edged Swords: Diaryl pyrazoline thiazolidinediones synchronously targeting cancer epigenetics and angiogenesis.

In the present study, two novel series of compounds incorporating naphthyl and pyridyl linker were synthesized and biological assays revealed 5-((6-(2-(5-(2-chlorophenyl)-3-(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-oxoethoxy) naphthalene-2-yl)methylene)thiazolidine-2,4-dione (14b) as the most potent dual inhibitors of vascular endothelial growth factors receptor-2 (VEGFR-2) and histone deacetylase 4 (HDAC4). Compounds 13b, 14b, 17f, and 21f were found to stabilize HDAC4; where, pyridyl linker swords were endowed with higher stabilization effects than naphthyl linker. Also, 13b and 14b showed best inhibitory activity on VEGFR-2 as compared to others.

Chemically characterized nanoencapsulated Homalomena aromatica Schott. essential oil as green preservative against fungal and aflatoxin B contamination of stored spices based on in vitro and in situ efficacy and favorable safety profile on mice.

Present study deals with the efficacy of nanoencapsulated Homalomena aromatica essential oil (HAEO) as a potent green preservative against toxigenic Aspergillus flavus strain (AF-LHP-NS 7), storage fungi, AFB, and free radical-mediated deterioration of stored spices. GC-MS analysis revealed linalool (68.51%) as the major component of HAEO.

Thiazolidinedione "Magic Bullets" Simultaneously Targeting PPARγ and HDACs: Design, Synthesis, and Investigations of their and Antitumor Effects.

Monotargeting anticancer agents suffer from resistance and target nonspecificity concerns, which can be tackled with a multitargeting approach. The combined treatment with HDAC inhibitors and PPARγ agonists has displayed potential antitumor effects. Based on these observations, this work involves design and synthesis of molecules that can simultaneously target PPARγ and HDAC.

Assessment of nanoencapsulated Cananga odorata essential oil in chitosan nanopolymer as a green approach to boost the antifungal, antioxidant and in situ efficacy.

In this study, a comparative efficacy of Cananga odorata EO (CoEO) and its nanoencapsulated formulation into chitosan nanoemulsion (CoEO-CsNe) against a toxigenic strain of Aspergillus flavus (AF-M-K5) were investigated for the first time in order to determine its efficacy in preservation of stored food from fungal, aflatoxin B (AFB) contamination and lipid peroxidation. GC and GC-MS analysis of CoEO revealed the presence of linalool (24.56%) and benzyl acetate (22.

Pharmacophore hybridization approach to discover novel pyrazoline-based hydantoin analogs with anti-tumor efficacy.

In search for new and safer anti-cancer agents, a structurally guided pharmacophore hybridization strategy of two privileged scaffolds, namely diaryl pyrazolines and imidazolidine-2,4-dione (hydantoin), was adopted resulting in a newfangled series of compounds (H1-H22). Herein, a bio-isosteric replacement of "pyrrolidine-2,5-dione" moiety of our recently reported antitumor hybrid incorporating diaryl pyrazoline and pyrrolidine-2,5-dione scaffolds with "imidazoline-2,4-dione" moiety has been incorporated. Complete biological studies revealed the most potent analog among all i.

Power of two: combination of therapeutic approaches involving glucose transporter (GLUT) inhibitors to combat cancer.

Cancer research of the Warburg effect, a hallmark metabolic alteration in tumors, focused attention on glucose metabolism whose targeting uncovered several agents with promising anticancer effects at the preclinical level. These agents' monotherapy points to their potential as adjuvant combination therapy to existing standard chemotherapy in human trials. Accordingly, several studies on combining glucose transporter (GLUT) inhibitors with chemotherapeutic agents, such as doxorubicin, paclitaxel, and cytarabine, showed synergistic or additive anticancer effects, reduced chemo-, radio-, and immuno-resistance, and reduced toxicity due to lowering the therapeutic doses required for desired chemotherapeutic effects, as compared with monotherapy.

Benzylidene thiazolidinediones: Synthesis, in vitro investigations of antiproliferative mechanisms and in vivo efficacy determination in combination with Imatinib.

Thiazolidinedione (TZD) has been an interesting scaffold due to its proven antidiabetic activity and encouraging findings in anticancer drug discovery. We synthesised benzylidene thiazolidinedione derivatives which exhibited excellent antiproliferative effects in chronic myeloid leukemic cells K562 and the most active compounds 3t and 3x had GI value of 0.9 and 0.

Permuted 2,4-thiazolidinedione (TZD) analogs as GLUT inhibitors and their in-vitro evaluation in leukemic cells.

Cancer is a heterogeneous disease, and its treatment requires the identification of new ways to thwart tumor cells. Amongst such emerging targets are glucose transporters (GLUTs, SLC2 family), which are overexpressed by almost all types of cancer cells; their inhibition provides a strategy to disrupt tumor metabolism selectively, leading to antitumor effects. Here, novel thiazolidinedione (TZD) derivatives were designed, synthesized, characterized, and evaluated for their GLUT1, GLUT4, and GLUT5 inhibitory potential, followed by in-vitro cytotoxicity determination in leukemic cell lines.

Synthesis and Biological Evaluation of Pyrazoline and Pyrrolidine-2,5-dione Hybrids as Potential Antitumor Agents.

In search of novel and effective antitumor agents, pyrazoline-substituted pyrrolidine-2,5-dione hybrids were designed, synthesized and evaluated in silico, in vitro and in vivo for anticancer efficacy. All the compounds exhibited remarkable cytotoxic effects in MCF7 and HT29 cells. The excellent antiproliferative activity toward MCF7 (IC =0.

Structure guided design and synthesis of furyl thiazolidinedione derivatives as inhibitors of GLUT 1 and GLUT 4, and evaluation of their anti-leukemic potential.

Cancer cells increase their glucose uptake and glycolytic activity to meet the high energy requirements of proliferation. Glucose transporters (GLUTs), which facilitate the transport of glucose and related hexoses across the cell membrane, play a vital role in tumor cell survival and are overexpressed in various cancers. GLUT1, the most overexpressed GLUT in many cancers, is emerging as a promising anti-cancer target.

Discovery of novel N-substituted thiazolidinediones (TZDs) as HDAC8 inhibitors: in-silico studies, synthesis, and biological evaluation.

Epigenetics plays a fundamental role in cancer progression, and developing agents that regulate epigenetics is crucial for cancer management. Among Class I and Class II HDACs, HDAC8 is one of the essential epigenetic players in cancer progression. Therefore, we designed, synthesized, purified, and structurally characterized novel compounds containing N-substituted TZD (P1-P25).

CSNet: A new DeepNet framework for ischemic stroke lesion segmentation.

Background And Objectives: Acute stroke lesion segmentation is of paramount importance as it can aid medical personnel to render a quicker diagnosis and administer consequent treatment. Automation of this task is technically exacting due to the variegated appearance of lesions and their dynamic development, medical discrepancies, unavailability of datasets, and the requirement of several MRI modalities for imaging. In this paper, we propose a composite deep learning model primarily based on the self-similar fractal networks and the U-Net model for performing acute stroke diagnosis tasks automatically to assist as well as expedite the decision-making process of medical practitioners.

Development of 1,2,4-Triazole-5-Thione Derivatives as Potential Inhibitors of Enoyl Acyl Carrier Protein Reductase (InhA) in Tuberculosis.

Tuberculosis (TB) ranks second, next to AIDS making it most formidable disease in the present age. One of the crucial enzymes involved in cell wall synthesis of , InhA (enoyl acyl carrier protein reductase), one of the crucial enzymes involved in cell wall synthesis of , has been authenticated as an effective target for anti-mycobacterial drug development. In the current work, novel derivatives of 1,2,4-triazole-5-thione rationally designed, synthesized and spectrally characterized as promising InhA inhibitors.

Discovery of 5-naphthylidene-2,4-thiazolidinedione derivatives as selective HDAC8 inhibitors and evaluation of their cytotoxic effects in leukemic cell lines.

Histone deacetylases (HDACs) are being explored as a therapeutic target for interventions in different types of cancer. HDAC8 is a class I HDAC that is implicated as a therapeutic target in various indication areas, including different types of cancer and particularly childhood neuroblastoma. Most previously described HDAC8-selective inhibitors contain a hydroxamate function as zinc binding group (ZBG) to confer potency.

Fabrication, characterization and practical efficacy of Myristica fragrans essential oil nanoemulsion delivery system against postharvest biodeterioration.

The present study deals with encapsulation of Myristica fragrans essential oil (MFEO) into chitosan nano-matrix, their characterization and assessment of antimicrobial activity, aflatoxin inhibitory potential, safety profiling and in situ efficacy in stored rice as environment friendly effective preservative to control the postharvest losses of food commodities under storage. Surface morphology of MFEO-chitosan nanoemulsion as well as encapsulation of MFEO was confirmed through SEM, FTIR and XRD analysis. In vitro release characteristics with biphasic burst explained controlled volatilization from nanoencapsulated MFEO.

A multidrug and toxic compound extrusion (MATE) transporter modulates auxin levels in root to regulate root development and promotes aluminium tolerance.

MATE (multidrug and toxic compound extrusion) transporters play multiple roles in plants including detoxification, secondary metabolite transport, aluminium (Al) tolerance, and disease resistance. Here we identify and characterize the role of the Arabidopsis MATE transporter DETOXIFICATION30. AtDTX30 regulates auxin homeostasis in Arabidopsis roots to modulate root development and Al-tolerance.

Antimicrobial activity, antiaflatoxigenic potential and in situ efficacy of novel formulation comprising of Apium graveolens essential oil and its major component.

The present study reports the formulation of Apium graveolens essential oil (AGEO) with its major components linalyl acetate (LA) and geranyl acetate (GA) (1:1:1) as a novel green preservative for protection of postharvest food commodities from fungal infestations, aflatoxin B (AFB) secretion, free radical generation and lipid peroxidation. The essential oil based novel formulation displayed considerable inhibitory action against fourteen food borne molds responsible for deterioration of stored food commodities, in addition to the most toxigenic strain of Aspergillus flavus (AFLHPR14) isolated from fungal and aflatoxin contaminated rice seeds. The observed higher efficacy of designed formulation was due to the synergistic action of essential oil and its major components.

Visible light-controlled NO generation for photoreceptor-mediated plant root growth regulation.

Nitric oxide (NO) is an essential redox-signaling molecule free radical, contributes a significant role in a diverse range of physiological processes. Photo-triggered NO donors have significant potential compared to other NO donors because it releases NO in the presence of light. Hence, an efficient visible light-triggered NO donor is designed and synthesized by coupling 2,6-dimethyl nitrobenzene moiety at the peri-position of 1, 8-naphthalimide.

The multitasking abilities of MATE transporters in plants.

As sessile organisms, plants constantly monitor environmental cues and respond appropriately to modulate their growth and development. Membrane transporters act as gatekeepers of the cell regulating both the inflow of useful materials as well as exudation of harmful substances. Members of the multidrug and toxic compound extrusion (MATE) family of transporters are ubiquitously present in almost all forms of life including prokaryotes and eukaryotes.