Efficient method for the synthesis of novel methyl 4-cinnolinecarboxylate.

A new method is designed for the synthesis of some novel methyl 3-aryl/alkyl-4-cinnolinecarboxylate with developed a general Richter cyclization through diazotization strategy of commercially available 2-aryl/alkyl ethynyl aniline and methyl acetate. Most substrates were achieved in moderate to excellent yields in one-pot procedures under mild reaction conditions.

A Novel Generative Adversarial Network-Based Approach for Automated Brain Tumour Segmentation.

Background: Medical image segmentation is more complicated and demanding than ordinary image segmentation due to the density of medical pictures. A brain tumour is the most common cause of high mortality. Objectives: Extraction of tumorous cells is particularly difficult due to the differences between tumorous and non-tumorous cells. In ordinary convolutional neural networks, local background information is restricted. As a result, previous deep learning algorithms in medical imaging have struggled to detect anomalies in diverse cells. Methods: As a solution to this challenge, a deep convolutional generative adversarial network for tumour segmentation from brain Magnetic resonance Imaging (MRI) images is proposed. A generator and a discriminator are the two networks that make up the proposed model. This network focuses on tumour localisation, noise-related issues, and social class disparities. Results: Dice Score Coefficient (DSC), Peak Signal to Noise Ratio (PSNR), and Structural Index Similarity (SSIM) are all generally 0.894, 62.084 dB, and 0.88912, respectively. The model's accuracy has improved to 97 percent, and its loss has reduced to 0.012. Conclusions: Experiments reveal that the proposed approach may successfully segment tumorous and benign tissues. As a result, a novel brain tumour segmentation approach has been created.

Development of bioactive 2-substituted benzimidazole derivatives using an MnOx/HT nanocomposite catalyst.

Benzimidazole is a vital moiety found in a wide range of naturally and pharmacologically active molecules. We prepared a proficient and facile manganese oxide-supported magnesium and aluminium-based nanocomposite catalytic framework using the deposition-precipitation method and characterised it with XRD, XPS, SEM, TEM, and TGA techniques. Following that, the catalyst was used in the green synthesis of highly functional 2-substituted benzimidazole derivatives in an ethanol-water solvent system at room temperature using various assorted benzaldehydes and o-phenylenediamine as substituents. The synthesised catalyst operates efficiently and is applicable to a wide range of electron-withdrawing and electron-donating substrates, resulting in good to excellent yields. The advantages of this process include the use of a greener solvent, high yield, high conversions, no use of additives or bases, a good TOF, and a shorter reaction time.

Molecular docking and physicochemical studies of 1,3-benzodioxole tagged Dacarbazine derivatives as an anticancer agent.

Cancer, the biggest cause of death globally, remains a tough illness despite enormous advances in therapy. In the present study, 1,3-benzodioxole-tagged dacarbazine derivates were investigated as microtubule inhibitors in order to control cancer as microtubules are involved in cell proliferation. The tubulin protein was analyzed and its structure was validated by various protein validation tools. The binding potential of 1,3-benzodioxole-based dacarbazine-tagged derivatives with tubulin was checked using molecular docking software HEX 8.0 CUDA and AutoDock Vina. Swiss ADME online Web server and pkCSM are used for studying pharmacokinetic and pharmacological studies of compounds. The docking analysis ADME studies displayed that Compounds 1 and 2 bind effectively with the tubulin protein and showed potential properties to use as a potent anticancer drug.

Conversion of Limonene over Heterogeneous Catalysis: An Overview.

The natural terpene limonene is widely found in nature. The (R)-limonene (the most abundant enantiomer) is present in the essential oils of lemon, orange, and other citrus fruits, while the (S)- limonene is found in peppermint and the racemate in turpentine oil. Limonene is a low-cost, low toxicity biodegradable terpene present in agricultural wastes derived from citrus peels. The products obtained from the conversion of limonene are valuable compounds widely used as additives for food, cosmetics, or pharmaceuticals. The conversion of limonene to produce different products has been the subject of intense research, mainly with the objective of improving catalytic systems. This review focused on the application of heterogeneous catalysts in the catalytic conversion of limonene.

Antimicrobial Peptide Designing and Optimization Employing Large-Scale Flexibility Analysis of Protein-Peptide Fragments.

The mankind relies on the use of antibiotics for a healthy life. The epidemic-like emergence of drug-resistant bacterial strains is increasingly becoming one of the leading causes of morbidity and mortality, which gives rise to design a potential antimicrobial peptide (AMP). Here, we have designed the potential AMP using the extensive dynamics simulation since protein-peptide interactions are linked to large conformational changes. Therefore, we have employed the advanced computational avenue CABS molecular docking method that enabled the flexible peptide-protein molecular docking with a large-scale rearrangement of the protein. Lead AMP was investigated against the wild-type (WT) and mutant-PBP5 (MT-PBP5) proteins (antiresistance property). AMP20 showed strong interactions with wtPBP5 and mtPBP5 and involvement of a large number of elements in interactions determined through an atomic model study. Full flexibility analysis showed the stable interaction of AMP20 with both the wild-type and mutant form of PBP5 with root-mean-square deviation (RMSD) values of ∼4.51 and 4.85 Å, respectively. Moreover, peptide dynamics showed involvement of all residues of AMP20 through contact map analysis, and extensive simulation confirmed the stable interaction of AMP20, with lower values of RMSD, radius of gyration, and root-mean-square fluctuation. This study paves the way for a potential approach to design the AMP with amino acid walking and large-scale conformational rearrangements of amino acids.

A new biocompatible ternary Layered Double Hydroxide Adsorbent for ultrafast removal of anionic organic dyes.

It would be of great significance to introduce a new biocompatible Layered Double Hydroxide (LDH) for the efficient remediation of wastewater. Herein, we designed a facile, biocompatible and environmental friendly layered double hydroxide (LDH) of NiFeTi for the very first time by the hydrothermal route. The materialization of NiFeTi LDH was confirmed by FTIR, XRD and Raman studies. BET results revealed the high surface area (106 m2/g) and the morphological studies (FESEM and TEM) portrayed the sheets-like structure of NiFeTi nanoparticles. The material so obtained was employed as an efficient adsorbent for the removal of organic dyes from synthetic waste water. The dye removal study showed >96% efficiency for the removal of methyl orange, congo red, methyl blue and orange G, which revealed the superiority of material for decontamination of waste water. The maximum removal (90%) of dyes was attained within 2 min of initiation of the adsorption process which supported the ultrafast removal efficiency. This ultrafast removal efficiency was attributed to high surface area and large concentration of -OH and CO32- groups present in NiFeTi LDH. In addition, the reusability was also performed up to three cycles with 96, 90 and 88% efficiency for methyl orange. Furthermore, the biocompatibility test on MHS cell lines were also carried which revealed the non-toxic nature of NiFeTi LDH at lower concentration (100% cell viability at 15.6 µg/ml). Overall, we offer a facile surfactant free method for the synthesis of NiFeTi LDH which is efficient for decontamination of anionic dyes from water and also non-toxic.

Biological Evaluation of Noscapine analogues as Potent and Microtubule-Targeted Anticancer Agents.

In present investigation, an attempt was undertaken to modify the C-9 position of noscapine (Nos), an opium alkaloid to yield 9 -hydroxy methyl and 9 -carbaldehyde oxime analogues for augmenting anticancer potential. The synthesis of 9-hydroxy methyl analogue of Nos was carried out by Blanc reaction and 9-carbaldehyde oxime was engineered by oxime formation method and characterized using FT-IR, 1H NMR, 13C NMR, mass spectroscopy, and so on techniques. In silico docking techniques informed that 9-hydroxy methyl and 9-carbaldehyde oxime analogues of Nos had higher binding energy score as compared to Nos. The IC50 of Nos was estimated to be 46.8 µM signficantly (P < 0.05) higher than 8.2 µM of 9-carbaldehyde oxime and 4.6 µM of 9-hydroxy methyl analogue of Nos in U87, human glioblastoma cells. Moreover, there was significant (P < 0.05) difference between the IC50 of 9-carbaldehyde oxime and 9-hydroxy methyl analogue of Nos. Consistent to in vitro cytotoxicity data, 9-hydroxy methyl analogue of Nos induced significantly (P < 0.05) higher degree of apoptosis of 84.6% in U87 cells as compared to 78.5% and 64.3% demonstrated by 9-carbaldehyde oxime and Nos, respectively. Thus the higher therapeutic efficacy of 9-hydroxy methyl analogue of Nos may be credited to higher solubility and inhibitory constant (K).

Biology of Heme: Drug Interactions and Adverse Drug Reactions with CYP450.

Heme is central to functions of many biologically important enzymes (hemoproteins). It is an assembly of four porphyrin rings joined through methylene bridges with a central Fe (II). Heme is present in all cells, and its synthesis and degradation balance its amount in the cell. The deregulations of heme networks and incorporation in hemoproteins lead to pathogenic state. This article addresses the detailed structure, biosynthesis, degradation, and transportation associated afflictions to heme. The article is followed by its roles in various diseased conditions where it is produced mainly as the cause of increased hemolysis. It manifests the symptoms in diseases as it is a pro-oxidant, pro-inflammatory and pro-hemolytic agent. We have also discussed the genetic defects that tampered with the biosynthesis, degradation, and transportation of heme. In addition, a brief about the largest hemoprotein group of enzymes- Cytochrome P450 (CYP450) has been discussed with its roles in drug metabolism.

Preclinical evaluation and molecular docking of 1,3-benzodioxole propargyl ether derivatives as novel inhibitor for combating the histone deacetylase enzyme in cancer.

Even after huge strides in medicine, cancer continues to be a formidable disease, which is slated to become the leading cause of death worldwide. The present study investigates the 1,3-benzodioxole and its propargyl ether derivatives as a novel histone deacetylase enzyme inhibitor in order to cure cancer, as aberrant expression of histone deacetylases (HDACs) is associated with carcinogenesis. Bioinformatics approaches were employed to carry out preclinical and pharmacological evaluations of designed benzodioxole derivatives. Furthermore, their interaction with HDAC-1 enzyme was studied through computational methods for their specific inhibitory effects and evaluated for their LD50 (oral rat acute toxicity) value. In addition to this work, three-dimensional (3D) structure of HDAC-1 enzyme was extracted and evaluated using various parameters including Ramachandran plot and molecular docking stimulation. In our study, we found that compound 7 and compound 9 have higher binding score than approved drugs (SAHA, TSA and VPA). Importantly, these compounds were found to possess good pharmacological and pharmacokinetic properties and can be considered as potent novel compound to combat the HDAC-1 enzyme to cure cancer. Compounds were also analyzed and validated with parameters like absorption, metabolism, excretion, toxicity and synthetic accessibility during the preclinical evaluation. This study paves way to search for novel and potent small chemical compounds for inhibiting HDAC-1 enzyme and in particular to combat the cancer progression by interrupting the cell cycle.

Exploring the interplay between autoimmunity and cancer to find the target therapeutic hotspots.

Autoimmunity arises when highly active immune responses are developed against the tissues or substances of one's own body. It is one of the most prevalent disorders among the old-age population with prospects increasing with age. The major cause of autoimmunity and associated diseases is the dysregulation of host immune surveillance. Impaired repairment of immune system and apoptosis regulation can be seen as major landmarks in autoimmune disorders such as the mutation of p53 gene which results in rheumatoid arthritis, bowel disease which consequently lead to tissue destruction, inflammation and dysfunctioning of body organs. Cytokines mediated apoptosis and proliferation of cells plays a regulatory role in cell cycle and further in cancer development. Anti-TNF therapy, Treg therapy and stem cell therapy have been used for autoimmune diseases, however, with the increase in the use of immunomodulatory therapies and their development for autoimmune diseases and cancer, the understanding of human immune system tends to become an increasing requirement. Hence, the findings associated with the relationship between autoimmune diseases and cancer may prove to be beneficial for the improvement in the health of suffering patients. Here in, we are eliciting the underlying mechanisms which result in autoimmune disorders causing the onset of cancer, exploration of interactome to find the pathways which are mutual to both, and recognition of hotspots which might play important role in autoimmunity mediated therapeutics with different therapies such as anti-TNF therapy, Treg therapy and stem cell therapy.