Recent Developments in Chemistry and Biochemistry Research Vol. 5

The present study reports the isolation and characterization of bergapten, a furocoumarin, as a major constituent in the root bark of Ficus exasperata, as well as its hypoglycemic activity. Despite the wide ethnomedicinal applications of Ficus exasperata, little is known about the active principles responsible for the observed biological effects, thus limiting opportunities for further therapeutic applications. Phytochemical investigation of extracts from the genus Ficus revealed the presence of several bioactive secondary metabolites, including flavonoids, alkaloids, phenolic acids, steroids, saponins, tannins, terpenoids, and coumarins. The bioassay-guided chemical investigation of F. exasperata root bark resulted in the isolation of a furocoumarin (D-1), which was shown to be partly responsible for the acclaimed anti-diabetic effect of the plant. It is thus research-worthy to unravel the precise mechanism of action of the molecule as a hypoglycemic agent, followed by rational structural modification to optimize it for potency and safety.

High rates of alcohol intake are frequently the cause of liver complications. The majority of alcohol-drinking citizens in industrialized and developing nations suffer from cirrhosis, fatty liver, liver fibrosis, and even hepatocellular cancer, among other liver issues. Creating symptomatic, safe medication to go through this is a new global problem. The primary goal of the research is to provide a symptomatic, safe medicine to lessen liver damage caused by ethanol. We created a multi-herbal formulation (AKSS-16-LIV01), which may be helpful in liver complications.  In this investigation, we try to reduce liver damage from a variety of toxicants. Swiss albino mice were split up into seven groups, and each group was subjected to ethanol-induced injury for several weeks before our herbal preparation was used to investigate a healing response. The groups include the normal control group (Group-I), the group treated with 50% v/v ethanol (Group-II), the groups pre-treated with AKSS16-LIV01 at a low dose of 100 mg/kg/day (Group-III), the group pre-treated with AKSS16-LIV01 at a middle dose of 200 mg/kg/day (Group-IV), the group pre-treated with AKSS16-LIV01 at a high dose of 400 mg/kg/day (Group-V), the group pre-treated with Sylimarin at 100 mg/kg/day (Group-VI), and the only group treated with AKSS16-LIV01 (400 mg/kg/day) (Group-VII).In the mice given ethanol, the results showed a marked increase in a number of biochemical parameters, lipid profile parameters, lipid peroxidation, nitric oxide (NO) concentration, nitric oxide synthase level, and pro-inflammatory cytokines, such as tumour necrosis factor (TNF-\(\alpha\)) and transforming growth factor (TGF-\(\beta\)1). However, ethanol significantly decreased the levels of tissue antioxidant enzyme activity (SOD, CAT, GSH, and GPx), serum total protein, total albumin, albumin globulin ratio, and tissue total antioxidant enzyme activity. The formulation (AKSS16-LIV01) was applied therapeutically at a dose that determined its effectiveness in suppressing all relevant parameters mentioned above, while also shielding the liver from ethanol-induced fibrogenesis. In addition to this gross morphology of the liver, the hepato-protective impact of the formulation in comparison to the usual medication Sylimarin was clearly supported by H&E liver histology and Masson trichrome and serius red analysis of the liver sections. According to the study's findings, a multi-herbal formulation that was designed (AKSS16-LIV01) and given at a dose of 400 mg/kg/day produced the best possible response to lessen ethanol intoxication. The results unmistakably show that AKSS16-LIV01 may be a safe and non-toxic drug that shields the liver from oxidative damage caused by ethanol and keeps levels of pro-inflammatory cytokines stable over time.

A series of novel 2, 6-diamino-9-methyl purine derivatives coupled with N-Phthaloyl and carboxamide derivatives of L-methionine at the C2 position were synthesized by coupling of 2, 6-diamino-9-methyl purine with N-protected Methionine using phosphorous oxychloride in pyridine. The synthesized compounds were characterized using different physicochemical analyses and IR, ¹H, ¹³C–NMR, MS. The compounds were screened for their in vitro antimicrobial activity and demonstrated significant activity against the tested organisms. These compounds may prove useful as CDK inhibitors.  

Carbohydrates are the most abundant macromolecules among the organic substances present in living organisms on Earth. Monosaccharide derivatives are essential in biological chemistry because of their ability to inhibit bacterial infections and produce physiologically active molecules. Designing innovative antibacterial medicines with new structural scaffolds to treat drug-resistant microorganisms is a pressing issue. This study aimed to determine the binding affinity of previously synthesized methyl \(\alpha\)-D-glucopyranoside (MDGP) derivatives by molecular docking and molecular dynamics, as well as their physicochemical and pharmacokinetic features. B3LYP/3-21G was utilized to perform density functional theory (DFT) calculations on the MDGP derivatives and to determine the partial atomic charge and molecular electrostatic potential (MEP). The antibacterial effects of the proposed derivatives were assessed using AutoDock's molecular docking investigation with Bacillus subtilis HmoB haem oxygenase. The binding affinity according to the molecular docking score for Derivatives 8-10 (-10.11, -10.41, and -12.20 kcal/mol) against the bacterial pathogen B. subtilis HmoB indicates that these derivatives are potential antibacterial agents. Furthermore, a 100-ns molecular dynamics simulation confirmed the stable conformation and binding behavior of the MDGP derivatives in a stimulating environment. Furthermore, in an in silico ADMET analysis, the toxicity and bioactivity characteristics of MDGP and its derivatives were estimated to evaluate their safe uses and anticipate the need for further study of clinical phases as therapeutic molecules utilizing software and an online database. Our proposed novel MDGP derivatives may demonstrate first-rate and superior pharmacological properties in medicinal chemistry, providing valuable information for future studies on their biological activity. This research may reveal the chemical, thermal, biological, and pharmacokinetic properties of MDGP derivatives.

We outline herein the protocols developed to synthesize a diverse array of organic compounds: from carbimidothioates, we successfully synthesized \(\beta\)-enaminones, 1,5-diaryl-1H-tetrazoles, and 1,3,4-oxadiazoles, each of which has potential applications in various fields including pharmaceuticals and materials science. From carbamimidothioates, our synthesis yielded both imidazoles and 1,5-disubstituted tetrazoles, thus expanding the scope of these nitrogen-rich heterocycles in medicinal chemistry. Additionally, the transformation of 2-oxo-ethanimidothioates into 2-amino-3-aryl-quinoxalines highlights a novel pathway for producing compounds that could be valuable in light-emitting devices and as pharmacological agents. This detailed investigation not only advances the field of synthetic organic chemistry but also sets the stage for future innovations in the synthesis and application of heterocyclic compounds.

Construction of a series of N'-arylidene-3-(4-phenyloxazol-2-yl)propanehydrazide 4a–4j was achieved through the development of an easy, effective, and environmentally safe method. Under moderate reaction conditions, each substrate was obtained in good yield. IR, ¹H NMR, ¹³C NMR, and mass analysis were used to characterize each prepared hydrazone. Moreover, an antimicrobial activity screen was conducted on compounds 4a–4j. The prepared compounds' anti-microbial properties were tested against four bacterial strains Bacillus cereus, Bacillus megaterium, Escherichia coli, Xanthomonas campestris, and Candida albicans. Compounds 4i, 4f, and 4a demonstrated superior activity against Xanthomonas campestris, the compounds 4j, 4a, and 4h demonstrated good activity against Bacillus megaterium, the compounds 4a–4j display moderate activity against Escherichia coli, and Candida albicans.

Hydrogen bonding interactions in low molecular weight alcohols or lower alcohol (viz. methanol and ethanol) with water molecules are quite common. But, due to the presence of bulky groups in higher alcohol (viz. propanol, butanol and pentanol etc.) and their isomers, the hydrogen bonding interactions between alcohol and water molecules is significantly different. In alcohol-water heterodimer complexes, water plays an important role in the stability of such a system, alcohol will be interacting with water molecules either as proton donor or proton acceptor mode. The aim of this study is to understand the Hydrogen Bonding Interaction and Structural Change in Some Aliphatic Alcohol-Water Complexes. We have studied the hydrogen bonding interactions between some aliphatic alcohol-water complexes by computational methods. All the models were constructed by using GaussView 5.0. The interaction energy (IE) and natural bond orbital (NBO) calculations for some common aliphatic alcohol-water complexes (e.g. methanol, ethanol, propanol, butanol and pentanol) and their isomers are computed by using the MP4 method. All alcohol-water complexes can form hydrogen bonds either through proton accepting or proton donor mode of interaction. Calculation of the interaction energy of such complexes reveals that the proton acceptor (RHO---H₂O) hydrogen bonding mode is always more favorable than that of the proton donor (ROH---H₂O) mode of interaction.

The rambutan plant (Nephelium lappaceum L.) empirically contains flavonoids. Flavonoid has many kinds of bioactivity which function as antipyretic, analgesic, and anti-inflammatory effects and can help reduce fevers. There have not been many studies conducted on rambutan seeds as a pain and fever reliever. Fever is a sign that the body is fighting infection or bacteria in the body, usually, the body temperature has increased greater than normal body temperature (> 37.2^oC). The purpose of this study was to prove the antipyretic activity of rambutan seed extract against white male mice induced by the DPT-HB-Hib vaccine. This study used an experimental method which was divided into 5 treatment groups, namely, negative control of 1% Na CMC, positive control of paracetamol 1.3 mg/20 g BW of mice, and three groups of rambutan seed extract doses of 37.5 mg, 75 mg, and 150 mg/20 g BW mice. Fresh rambutan fruit was taken from Cikalang Tengah village, Tawang sub-district, Tasikmalaya City. Temperature measurements were carried out for 180 minutes with 30-minute intervals. The data obtained were analyzed by ANOVA test and LSD test. ANOVA test results for 180 minutes obtained p-value = 0.035, which means that there is a significant difference in temperature reduction in the five treatment groups, while the LSD test results for 180 minutes, the most effective dose is dose II of 75 mg/20 g BW in mice compared to other doses and did not have a significant difference with the positive control (paracetamol) because it had a comparable effect in reducing fever temperature in mice (Mus musculus). The dose III for 150mg/BW has an effectiveness rate of 98.11%. The highest antipyretic effectiveness falls to dose II for 75 mg/20g BW (98.58%), and the results are statistically significant.

A tetravalent peptide with the functional sequence NPSHPLSG designated svH1C, binds with high avidity to lectin-type receptors specific for structures that contain sialic acid (5-acetylneuraminic acid, Neu5Ac). Among the sialic acid-binding immunoglobulin-like lectins (the Siglec family of receptors), the peptide binds preferentially to those that bind Neu5Ac(\(\alpha\)2,3)Gal and Neu5Ac(\(\alpha\)2,8) Neu5Ac(\(\alpha\)2,3)Gal sequences and the larger sialyl Lewis^x (sLe^x) structure.  svH1C has a flexible structure that enables binding with high avidity in the glycan binding site in an ‘induced-fit’ conformation.  Peritoneal populations of cells in C57BL/6 mice that constitute the innate immune system were increased 2- to 6-fold after three alternate-day subcutaneous injections. Incubation of neuraminidase-treated, human peripheral blood mononuclear cells with biotin-tagged svH1C resulted in substantial binding of the peptide to a subset of the CD14⁺ monocyte population. Nanomolar concentrations of svH1C induced phagocytic activity of adherent cells (monocytes and macrophages) from PBMC cultures. Predictions by molecular modeling suggest that the peptide binds to P- and E-selectins, which are receptors that facilitate the migration of neutrophils and T cells through endothelial tissues, and to siglecs on macrophages with avidities that are expected to mitigate neutrophil-driven inflammation. The therapeutic value of these anti-inflammatory activities was demonstrated by the resolution of severe lipopolysaccharide-induced inflammation in the skin of mice in two weeks by daily subcutaneous injections of 1 nmol/g body weight. These results support the conclusion that svH1C mimics Neu5Ac(\(\alpha\)2,3) Gal sequences and interacts with glycan binding sites of specific receptors with avidities sufficient to promote repair and restoration of damaged tissues.

The present study aimed to determine the extraction of some bioactive phytochemical constituents from flaxseed by Gas Chromatography-mass Spectrometry (GC-MS) and Atomic Absorption method. Flaxseed (Linum usitatissimum L.) is an important source of oil. The dried seed of flaxseed 100 g, produced 38% of oil extracted by n-hexane, the physiochemical properties of flaxseed such as acid value (0.71 mg KOH/g) as oleic acid, peroxide value (2.69 meq O2/kg), saponification value (186.50 mg KOH/g oil), and iodine value (96.67 g/100 g), density (0.91 g/cm3), refractive index (1.39 and at 28°C), viscosity (CST) (68.33). Flaxseed oil is the richest plant source of oleic, linoleic (omega-6), and linolenic (omega-3) polyunsaturated fatty acids (PUFA), which are essential for humans. Gas Chromatography-Mass Spectrometry (GC-MS) was used to identify bioactive phytochemical constituents in flaxseed. 26 compounds were identified, the major compounds were 9-Octadecenoic acid (Z), (Oleic acid) (43.72) act as antioxidants, anti-cancer, Hexadecanoic acid, (Palmitic acid) (17.36) act as anti-oxidant, decrease blood cholesterol, anti-inflammatory, 9,12,15-Octadecatrienoic acid, (Z,Z,Z) fatty acids:\(\alpha\)-Linolenic acid, an omega-3 (n-3) fatty acid \(\gamma\)-Linolenic acid, an omega-6 (n-6) fatty acid (15.72); Octadecanoic acid Methyl stearate (13.13) used as a food additive, soaps, cosmetics, detergents lubricants, softening and release agents;13-Docosenoic acid, methyl ester, (Z)-(1.31); and cis-11-Eicosenoic acid, methyl ester (0.96) act as antibacterial, antitumor, antifungal, and cytotoxic agents. Atomic absorption is used to identify mineral content. It contains Calcium 1180ppm, Copper 4.1ppm, Ferric 15.7ppm, Zinc 34.58ppm. It is concluded that Flaxseed (Linum usitatissimum L.) is beneficial in the chemical composition used as food oil and contains bioactive compounds with antimicrobial, antiradical, antioxidant, and anticancer properties.