Advancement and development in computational chemistry for Colorectal Cancer diagnosis and treatment

: Colorectal cancer is the third most common form of cancer in the world and is a significant cause of death from cancer. To get a cure for colorectal cancer, early diagnosis and screening are necessary, as well as a clear understanding of the molecular basis of the disease. Molecular characterization of mutations associated with cancer provides useful information on the prognosis and reaction to therapy. This review discusses the clinical, molecular, and pathogenic features of the early onset of colorectal cancer, its screening tests, and diagnosis. The recent advances and rapid growth of computational tools in colorectal cancer used for diagnosis as well as screening are outlined in this review, including artificial intelligence, computer aided diagnosis, molecular docking, machine learning, and deep learning. In recent developments, the application of artificial intelligence has proved its excellency and shown a promising result, pointing out the severe need for a multidisciplinary approach to achieve an excellent result.

Flavaglines: Discovery From Plants Used in Traditional Chinese Medicine, Synthesis and Drug Development against Cancer and Immune Disorders

: Flavaglines, a family of compounds coming from plants used in Traditional Chinese Medicine, exhibit a broad range of biological effects including anticancer, antiviral, cardioprotectant and anti-inflammatory activities. They exert their action by targeting the scaffold proteins called prohitins-1 and-2, and the mRNA helicases eIF4A and DDX3. Flavaglines are densely functionalized cyclopenta[b]benzofurans that have attracted the attention of some of the most eminent organic chemists. This review provides an overview of the biosynthesis, total synthesis and pharmacological activities of flavaglines, which recently culminated with the entrance of a synthetic derivative, Zotatifin, into clinical trials against advanced solid tumors refractory or intolerant to standard treatments.

MnO, Co and Ni Nanoparticle Synthesis by Oleylamie and Oleic Acid

Background: Magnetic nanoparticles are attracting much attention toward easy operation and size controlable synthesis methods. We develop a method to synthesize MnO, Co, CoO, and Ni nanoparticles by thermal decomposition of metal 2,4-pentanedionates in the presence of oleylamine (OLA), oleic acid (OA), and 1‐octadecene (ODE). Methods: Similar experimental conditions are used to prepare nanoparticles except for the metal starting materials (manganese 2,4-pentanedionate, nickel 2,4-pentanedionate, and cobalt 2,4-pentanedionate), leading to different products. For the manganese 2,4-pentanedionate starting material, MnO nanoparticles are always obtained as the reaction is controlled with different temperatures, precursor concentrations, ligand ratios, and reaction time. For the cobalt 2,4-pentanedionate starting material, only three experimental conditions can produce pure phase CoO and Co nanoparticles. For the nickel 2,4-pentanedionate starting material, only three experimental conditions lead to the production of pure phase Ni nanoparticles. Results: The nanoparticle sizes increase with the increase of reaction temperatures. It is observed that the reaction time affects nanoparticle growth. The nanoparticles are studied by XRD, TEM, and magnetic measurements. Conclusion: This work presents a facile method to prepare nanoparticles with different sizes, which provides a fundamental understanding of nanoparticle growth in solution.

Synthesis, Characterization, and Application of Chalcone Derivatives as Chemosensors for Cyanide Anions

Research Background: The extreme toxicity of cyanide ions to living organisms encourages the researcher to develop new chemosensors for their sensitive and selective detection. Among various classes of chemosensors, chalcones are believed to be a promising candidate for designing new chemosensors for anions due to easy modification in its skeleton and conjugation system. Research Gap and Problem Statement: Despite having various medical applications and properties, the recognition ability of chalcone derivatives is not widely explored. The traditional methods known for the sensing of cyanide ions are ion chromatography or cyanide selective electrodes. However, these methods need skilled operators and are found to be expensive and time-consuming. Also, the available methods for detection of cyanide ions are not suitable for on-site monitoring and show interference from other competitive anions such as fluoride, acetate, and hydroxide ions. Hence, this encouraged us to explore the chalcone derivatives as chemical sensors that are capable of detecting the cyanide ions in presence of competitive anions such as fluoride, acetate, and hydroxide ions. Objectives of the study: The development of new chalcone analogs (1E,4E)-1,5-bis(4-chlorophenyl)penta-1,4-dien-3-one (3) and (E)-3-phenyl-1-(pyridin-2-yl)prop-2-en-1-one (6), which are particularly important for the future development of chemosensors for the detection of cyanide ions in presence of various interfering ions such as fluoride, acetate, and hydroxide ions. Methods: The sensing behavior of chalcone derivatives (1E,4E)-1,5-bis(4-chlorophenyl)penta-1,4-dien-3-one (3) and (E)-3-phenyl-1-(pyridin-2-yl)prop-2-en-1-one (6) have been investigated toward various anions (CN-, F-, Cl-, Br-, NO3-, SO42-, PO42-, OH-, OAc-) using UV-vis spectroscopy. Interestingly, among various anions tested, derivatives (1E,4E)-1,5-bis(4-chlorophenyl)penta-1,4-dien-3-one (3) and (E)-3-phenyl-1-(pyridin-2-yl)prop-2-en-1-one (6) function as highly selective chemosensors for the detection of cyanide ions. Results: We have synthesized two chalcone based derivatives (1E,4E)-1,5-bis(4-chlorophenyl)penta-1,4-dien-3-one (3) and (E)-3-phenyl-1-(pyridin-2-yl)prop-2-en-1-one (6) with simple condensation reaction for the detection of cyanide ions. The various results indicated the quick response of (1E,4E)-1,5-bis(4-chlorophenyl)penta-1,4-dien-3-one (3) and (E)-3-phenyl-1-(pyridin-2-yl)prop-2-en-1-one (6) toward cyanide anions. These two chalcone derivatives (1E,4E)-1,5-bis(4-chlorophenyl)penta-1,4-dien-3-one (3) and (E)-3-phenyl-1-(pyridin-2-yl)prop-2-en-1-one (6) showed not only spectral change with selectivity but also showed sensitivity for the detection of cyanide anions. The developed chalcone derivatives (1E,4E)-1,5-bis(4-chlorophenyl)penta-1,4-dien-3-one (3) and (E)-3-phenyl-1-(pyridin-2-yl)prop-2-en-1-one (6) detect cyanide ions in presence of various interfering ions such as fluoride, acetate, and hydroxide ions. The chemosensors (1E,4E)-1,5-bis(4-chlorophenyl)penta-1,4-dien-3-one (3) and (E)-3-phenyl-1-(pyridin-2-yl)prop-2-en-1-one (6) for the detection of cyanide ions are particularly smart due to their real-time analysis, simplicity, and low cost in comparison to other closely related processes such as fluorescence. Conclusion: The sensitivity studies show the high reactivity of derivative 1,5-bis(4-chlorophenyl)penta-1,4-dien-3-one (3) as compared to (E)-3-phenyl-1-(pyridin-2-yl)prop-2-en-1-one (6). The detection limit for derivatives (1E,4E)-1,5-bis(4-chlorophenyl)penta-1,4-dien-3-one (3) and (E)-3-phenyl-1-(pyridin-2-yl)prop-2-en-1-one (6) was 1.2 µM and 300 µM, respectively. The results of (1E,4E)-1,5-bis(4-chlorophenyl)penta-1,4-dien-3-one (3) and (E)-3-phenyl-1-(pyridin-2-yl)prop-2-en-1-one (6) for cyanide detection were satisfying and suggesting their potential application for cyanide detection. Future direction: Further research of this field is to develop water soluble chalcone based probes, which show emission in the Near Infra-Red (NIR) region to provide favorable conditions for biological applications.

Medicinal importance, pharmacological activities and analytical aspects of canadine in the medicine: An important phytochemical of Hydrastis canadensis

Background: Natural products and their derived phytochemicals have been used in the medicine and gaining importance in the modern medicine due to their therapeutic potential and health beneficial effect on human disorders. Plenty of herbal drug based products are available in the market and playing an important role in the human health care system due to their health beneficial properties in human being. In the modern age we can find many herbal based products in the market mainly prepared from the natural products and used for the prevention and treatment of various human disorders. Benzylisoquinoline alkaloids are the important class of alkaloidal compounds and the better example are morphine, codeine, sanguinarine, berberine and canadine which are mainly known for their medicinal value in the medicine. Methods: Hydrastis canadensis is the important medicinal plant found to contain a significant amount of canadine, hydrastine and berberine. In the present investigation, numerous scientific databases such as Google, Pubmed, Science direct etc. have been searched to collect the important scientific information of canadine and analyzed to know the health beneficial aspect of canadine in the medicine. All the collected scientific information data’s were analyzed and have been categorized into mainly pharmacological and analytical aspects. Results: From the analysis of the collected scientific information, it was found that Hydrastis canadensis contain significant amount of canadine with many more phytochemical including canadaline, hydrastidine, isohydrastidine etc. Pharmacological activity data analysis revealed the biological importance of Hydrastis canadensis in the medicine for their traditional uses against gastritis, colitis, duodenal ulcers, loss of appetite, liver disease, bile secretion disorder, snake bites and vaginitis in the medicine. However, scientific data analysis of canadine revealed their effectiveness for their acetylcholinesterase inhibitory activity, anti-cancer, anti-microbial, anti-allergic activity and anti-oxidant activity. Different modern analytical tools have been used in the modern medicine for the isolation and quantification of canadine in the Hydrastis canadensis. Conclusion: Present investigation revealed the medicinal importance and pharmacological activities of a canadine in the medicine for the treatment of numerous human health complications. These scientific data will be helpful to the scientist to know the biological importance of canadine in the medicine against various forms of human complications.

The Role Of Polyvinylpyrrolidone as a Potential Fluorophore for the Detection Of Nitroaromatic Explosives.

Background: Detection of explosives (Nitroaromatic compounds) is one of the major issues faced in global security and to date remains a challenge even though some materials are developed for their detection. This study introduces the use of polyvinylpyrrolidone (PVP), a non-conjugated conducting polymer as a potential fluorophore for sensing nitroaromatics. The stimuli - response of fluorescence of PVP on interaction with energetic nitroaromatics was investigated in the present study. Methods: Fluorescence quenching studies of 5% PVP was carried out by the addition of varying concentration of quenchers (m-dinitrobenzene, trinitrobenzene and 2,4,6-trinitrophenol). To study the effect of different solvents on fluorescence quenching, two different solvents were used i.e., water and ethanol. The quenching studies of PVP with dinitrobenzene and trinitrobenzene was carried out in ethanol and 2,4,6-trinitrophenol was carried out in water. Results: The maximum emission peak intensity of PVP was observed at 445nm in ethanol and 420nm in water which was quenched upon gradual addition of quenchers. This shift in maximum peak intensity of PVP was understood from the change in the solvent polarity. UV-Visible and FT-IR studies were also carried out to understand the nature of interaction taking place between the quenchers and PVP. The limit of detection (LOD) was observed as 1.8x10-3M, 2.5x10--6M, and 3.9x10-6 M for picric acid, dinitrobenzene andtrinitrobenzene respectively. Conclusion: The results envisage PVP as a potential candidate for sensing energetic nitroaromatics with good sensitivity.

C-Methylation Of Organic Substrates. A Comprehensive Overview. Part Iva. Methylating Agents Other Than Methane, Methanol, And Methyl Metals

: C-Methylation of organic substrates was accomplished with a number of methylating agents other than methane, methanol, and methyl metals. They include methyl halides (MeX, X = I, Br, Cl, F), methyl-containing halogenated reagents, methyl peroxides, dimethyl carbonate (DMC), dimethylsulfoxide (DMSO), N,N-dimethyl formamide (DMF), diazomethane, formate salts, trioxane, CO/H2, CO2/H2, and dimethyl ether (DME). Under particular conditions, some methyl-containing molecules such as polymethylbenzenes, methylhydrazine, tris(diethylamino)sulfonium difluorotrimethylsilicate, methyl tosylate, long-chain alkyl alcohols, and acetic acid unexpectedly C-methylated a variety of organic substrates. A few cases of C-methylation only were reported to occur in the absence of catalysts. Otherwise, transition metal complexes as catalysts in conjunction with specific ligands and bases were ubiquitously present in most C-methylation reactions. Of the reactions, Suzuki-Miyaura-type cross-coupling remained of paramount importance in making 11CH3-bearing positron emission tomography tracers (PETs), one of the best applications of such methylation. Methylation proceeded at C(aromatic)-X, C(sp3)-X C(sp2)-X, and C(sp)-X of substrates (X = H, halogen). Ortho-methylation was regioselectively observed with aromatic substrates when they bear moieties such as pyridyl, pyrimidyl, amide, and imine functionalities, which were accordingly coined ‘ortho-directing groups’.

Bioanalytical Method Development and Validation of Cilnidipine and Metoprolol Succinate by RP-HPLC: Its Pharmacokinetic Application

Background: Cilnidipine and Metoprolol Succinate are antihypertensive agents used in the treatment of hypertension. Methods: Pharmacokinetic study of Cilnidipine and Metoprolol Succinate in rat plasma was carried out using the chromatographic method. The Chromatographic method was achieved on a reversed-phase C18 column, using acetonitrile and pH 4.0 water as ratio of 80:20 v/v as mobile phase, and a flow rate of 1.2 ml/min, and UV detection at 231 nm. In-vivo pharmacokinetic studies were performed on rats. Rats were treated with Cilnidipine (1mg/kg) and Metoprolol Succinate (1 mg/kg) orally, and blood samples were collected (0), 0.5, 1, 2, 4, 6, 8, 12, and 24 h post-treatment. Results: The retention time of Plasma, Cilnidipine, and Metoprolol Succinate were found to be 2.3, 3.1, and 5.5 min, respectively. Linearity was acceptable in the concentration range of 2-10 and 10-50 for Cilnidipine and Metoprolol Succinate, respectively. The intra-day and inter-day variance was less than 2. The mean recovery of Cilnidipine and Metoprolol Succinate were 100.12 and 100.15, respectively. The assay was successfully applied to a pharmacokinetic study in the rat after oral administration. After oral administration, maximal concentration (Cmax) of Cilnidipine and Metoprolol Succinate being 460.01 and 642.13 (μg g/mL), half-life found at 2.0 and 3.904 hours, respectively. Conclusion: The present method was successfully applied to a pharmacokinetic study of Cilnidipine and Metoprolol Succinate in rat plasma after oral administration.

Spectral, Crystalline, Thermal, Morphological characterization and Catalytic Performance of Ruthenium(III) Complexes of Natural Biopolymer Based on Schiff base Ligands

Aims: The aim of this study is to achieve catalytic performance for oxidation of alcohols using Ruthenium(III) metal complexes as a catalyst. Background: The chitosan is a potential candidate which enables synthesis of transition metal complexes from its corresponding bidentate ligands. Method: The chemical modification was performed on chitosan molecule with suitable aldehydes. The oxidation of alcohols was performed using ruthenium metal complexes as catalysts with Pyridinium chlorochromate (PCC) as oxidant and dichloro methane as solvent. To a solution of alcohol (2mmol) in dichloromethane (25mmol), Pyridinium chlorochromate (3 mmol) and Ruthenium(III) complexes (0.01mmol) were added. The solution was stirred for 12 h at room temperature. At the required time, the aldehyde / ketone was extracted with n-hexane. Then hexane was analyzed by GC. Results: The ruthenium(III) complexes derived from modified chitosan Schiff bidentate ligands resulted in good catalytic performance for oxidation of alcohols under optimized conditions. Conclusion: The enhanced catalytic activities of ruthenium(III) complexes were due to the presence of electron donating groups in the Schiff base ligand. : Ruthenium(III) complexes [Ru(CS)4hy3mbd)(H2O)2Cl2] and [Ru(CS)2hybd)(H2O)2Cl2] have been synthesized and characterized by FT-IR, X-ray diffraction, Thermo-gravimetric analysis and SEM with EDX. The ruthenium complexes were derived from chitosan biopolymer based Schiff base ligands. The N and O donor atoms of chitosan Schiff base ligands were involved in complexation reaction with Ruthenium metal ion to form stable coordination complex. This synthesized Ruthenium(III) complexes acted as active catalyst for the oxidation of primary and secondary alcohols which has converted to corresponding aldehydes and ketones at suitable reaction conditions. The oxidation of alcohols was performed using ruthenium metal complexes as catalyst with Pyridinium chlorochromate (PCC) as oxidant and dichloro methane as solvent.