Current Bioactive Compounds - Volume 20, Issue 2, 2024

Background: Antimicrobial resistance against pathogenic bacterial strains is the current problem faced by the world. Medicinal plants are being focussed for new alternatives to routine antibiotics for novel therapeutic and antimicrobial approaches. Objective: In this present study, fennel extract from Foeniculum vulgare plant was investigated against methicillin-resistant Staphylococcus aureus (MRSA). Method: Ethanol extraction of fennel seeds was performed and minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and time-kill curve was studied to find antimicrobial activities. Biofilm eradication was estimated by crystal violet assay. Result: Antimicrobial study showed a MIC of 500 μg/ml and MBC of 1000 μg/ml for fennel extract. Sub-inhibitory concentrations (½ MIC and ¾ MIC) started to kill bacterial cells after the addition of fennel extract at mid-log phase of growth. Test phytochemical eradicated 38.7%, 62.2%, and 76.9% of MRSA biofilm from microtitre plate when added at a concentration of 250 μg/ml, 375 μg/ml and 500 μg/ml, respectively. Conclusion: This study showed different bactericidal and antibiofilm activity of fennel seed extract against MRSA. We suggested that the phytocompound could be a promising candidate and further investigation is needed to isolate the active component of the extract for the management of MRSA.

Background: Depression is one of the most common neurological disorders for which only symptomatic treatment is available with synthetic drugs with serious side effects. Allicin [S- (2-propenyl)-2-propene-1-sulfinothioate] is a bioactive component derived from Allium sativum L. (Garlic). It has the property to penetrate the blood-brain barrier, which reveals its neuroprotective property. A synthetic drug named fluoxetine (selective serotonin re-uptake inhibitor) was introduced for the clinical treatment of depression. It is a selective serotonin re-uptake inhibitor that is well absorbed after oral administration. Aims and Objectives: This study aimed to evaluate the anti-depressant effect of fluoxetine alone and in combination with allicin. Methods: A pharmacokinetic study of allicin alone as well as in combination with fluoxetine was conducted to evaluate peak concentration, peak concentration time, and area under the curve in blood plasma. Furthermore, the biochemical analysis of neurotrophin levels of brain-derived neurotrophic factor (BDNF), serotonin, and dopamine was also performed to determine the antidepressant activity with synergism effect of allicin and fluoxetine. Results: The results of a pharmacokinetic study for co-administration of fluoxetine with allicin and enhanced neurotrophins and monoamines levels confirmed their effectiveness against depression. They may also be effective in suicidal risk associated with anti-depressant drugs. Conclusion: A combination of synthetic drugs with herbal compounds may be an alternate and effective therapy to overcome harmful effects.

Background: Glycosylamine play an important role in living organisms. Most plants store their chemical resources in the form of inactive glycosides, which are broken down and converted into sugar in the body of herbivores by hydrolyzing enzymes. Glycosylamine are obtained from the secondary metabolism of plants and consist of two parts. One part of it contains sugar like glucose and is inactive in most substances, and has a good effect on the solubility of the glycosylamine derivatives and its absorption and even its transfer from one organ to another. The therapeutic effect is related to the second part, which is called aglycan (or aglucan). Glycosylamine derivatives form a large group of valuable medicinal substances, which at the same time include some of the most dangerous and toxic substances in nature. These substances are present in many groups of flowering plants. Glycosides are made in different ways in different metabolic pathways. These materials have a complex and special chemical structure and leave special effects on the human body. Glycosylamine derivatives are called O-glycosid, N-glycosid, S-glycosid in terms of atoms coupling to anomeric carbon. Carbohydrate esterification reaction to prepare new glycosylamine derivatives is one of the most important carbohydrate reactions. The anomeric position of carbohydrates with strong leaving groups is very important for the preparation of glycosides. Preparation of glycosylamine derivatives based on acetylated carbohydrates is the main purpose of this article. Different carbohydrates were acetylated under mild conditions and high yields. The anomeric position was deacetylated by a magnesium oxide heterogeneous catalyst in methanol solvent. In order to prepare new glycosides acetylated/ deacytylated carbohydrate reacted with N-Methyl-(naphtha-2- ylmethoxy)amine. The final product was identified by various spectroscopic methods. Methods: Anhydrous sodium acetate (4 g) and α-D-glucose (28 mg, 5 g) were mixed. The mixture was transferred to a 200 ml Round-bottom flask . Acetic acid (260 mg, 25 ml) was added to the reaction mixture. The reaction mixture was heated in a boiling water bath for 2 h until complete dissolution of the glucose. Then 100 ml of ice was added. After 1 hour, White crystals formed and were washed with cold water. And then 1 mol of glucose pentaacetate per 50 ml of methanol was dissolved by a magnetic stirrer. After thatMgO (0.2gr) was added to the reaction mixture. The reaction mixture was refluxed at room temperature within 4-5 hours. After 5 hours, the solvent was removed and separated by chromatography. It is then washed with hexane and crystallized by etherhexane. And the final step reacted with N-Methyl- (naphtha-2-ylmethoxy) amine in order to prepare new glycosylamine derivatives. Results: Magnesium oxide in methanol solvent is one of the best effective catalysts in the deacetylation of the anomer position of acetylated carbohydrates. It is done under ambient temperature and in very easy conditions and makes carbohydrates susceptible to extensive chemical reactions. One of these reactions is the formation of glycosides. Various carbohydrates are acetylated by acetic anhydride in the presence of sodium acetate, and the anomeric position is deacetylated by a heterogeneous catalyst. In order to prepare N-glycoside, the glycosides are reacted with N-alkoxy N-methylglycosyl amine. The final products are identified by various spectroscopic methods. Conclusion: Glucose, mannose, for example, were acetylated by acetic anhydride in the presence of sodium acetate. And the anomeric position of pentaacetate glucose was selectively deacetylated with magnesium oxide in a methanol solvent. Then, the reaction for the preparation of glycosylamine derivatives was carried out under very mild and easy conditions. The aminoglycosides synthesized in this article are used as raw materials for the synthesis of a wide range of antibacterials.

Piperazine is the heterocyclic nucleus and exhibits significant biological potential such as antipsychotic, antidepressant, antihistamine, anticancer, anti-anginal, cardioprotective, antiviral, and anti-inflammatory activity. As a result, it had been considered a crucial structural component in the majority of the therapeutic medications that were already on the market. Other issues that limit its use include solubility, limited bioavailability, cost-effectiveness, and a mismatch between the drug's pharmacokinetic and pharmacodynamic profiles. Literature describes structural modification in the piperazine moiety to create novel derivatives or analogues to solve the issues with currently marketed medications. Nature provides various bioactive components having piperazine nuclei in their core structure. The present review describes the potential of the piperazine nucleus present in natural bioactive components. So the study concludes that it is vital to concentrate on the structural characteristics of this scaffold, which opens the way for future research and may benefit pharmaceutical companies as well as medicinal chemists.

Background: One-pot synthesis of new and biologically important betulinic acid derivatives has been designed and efficiently achieved in this work. Methods: The utilization of the carboxylic and hydroxyl moieties of betulinic acid has resulted in the development of a one-pot strategy towards the synthesis of some target compounds. Results: One-pot synthesis of new betulinic acid derivatives 3-9 has been achieved in moderate to high yields by way of esterification of the carboxylic functionality with a variety of alkylating agents. These were fully characterized by spectroscopic techniques. Conclusion: The synthesized new derivatives of betulinic acid were screened for their cytotoxic effect against human pancreatic cancer cells.

Background: Pyrazolidine 5,3-dione derivatives have a wide range of biological and pharmacological activities and play an important role in the sub-structures of various drugs. They also have inhibitory and antimicrobial properties, anti-tumor, anti-inflammatory, analgesic, antituberculosis, anti-hypertensive, anti-cancer, and anti-Alzheimer. The purpose of the current study was to investigate a number of synthesis methods of pyrazolidine-3,5-dione and 1 phenylpyrazolidine- 3,5-dione in the presence and absence of ultrasound bath and their anti-cancer effects on mcf-7 breast cancer cells. Methods: In this study, pyrazolidine-3,5-dione and 1-phenylpyrazolidine-3,5-dione were synthesized using hydrazine, phenylhydrazine, and diethyl malonate by different methods. The advantage of this research compared to other studies is the use of different methods (3 methods and each method were performed in two different conditions, toalling 6 methods) for the synthesis of these two derivatives. The effect of two synthesized derivatives on MCF-7 cell line breast cancer cells was also investigated using MTT (methylthiazole tetrazolium) test. IR, 13CNMR, and HNMR spectroscopy methods have also been used to determine the structure of products. Results: The results of FT-IR and NMR spectrum analysis confirm the synthesized pyrazolidine- 3,5-dione and 1-phenylpyrazolidine-3,5-dione. Based on the results in zero doses (control group) and 10 μM of all Samples after 24 hours, no significant difference in the number of cells was observed. However, the number of cells significantly decreased after treatment with 20 μM dose of both pyrazolidine-3,5-dione and 1-phenylpyrazolidine-3,5-dione. Also, there was no significant difference in reducing cancer cell proliferation between pyrazolidine-3,5-dione and 1-phenylpyrazolidine-3,5-dione samples. In addition, treatment of cancer cells with 40 μM of both hydrazine and phenylhydrazine samples after 24 hours caused approximately 50% cell death and reduced the number of cancer cells by approximately half compared to the control group. Conclusion: According to the results of this study, treatment of cancer cells with a dose of 40 μM in both samples of pyrazolidine-3,5-dione and 1-phenylpyrazolidine-3,5-dione after 24 hours caused cell death in approximately 50% of cells and the number of cancer cells is almost half that of the control group.

Background: Curcumin, a polyphenol compound, is reported to exhibit ameliorative effects in acute lung injury and different organ fibrosis models. We have previously demonstrated that curcumin, at a dose of 75 mg/kg, could modulate inflammatory mediators and fibrinolytic system proteins in the inflammatory stage as well as fibroproliferative stage in a mouse model of bleomycin (BLM) induced pulmonary fibrosis. In this study, we investigated the efficacy of the same dose of curcumin in resolving the established fibrotic stage in a mouse model of BLM-induced pulmonary fibrosis. Methods: We prepared the fibrosis model by intranasal administration of BLM (2 mg/kg). Curcumin intervention was performed by intraperitoneal injection on 16th to 20th days post BLM exposure. The control group was administered with normal saline. The mice were sacrificed on the 21st day post BLM exposure. Results: Histological analysis of the lung tissue samples indicated that curcumin (75 mg/kg) could not reverse the fibrotic features induced by BLM. We also performed RT-PCR and western blot to examine the molecular changes induced by BLM and curcumin. It was observed that curcumin could neither reduce the expressions of fibrotic markers nor restore the normal expressions of proteins in the fibrinolytic system. Conclusion: Our data suggest that a low dose of curcumin is not effective in ameliorating the fibrotic stage of BLM-induced pulmonary fibrosis. An increased dose or a formulation that increases the bioavailability of curcumin could probably exhibit promising effects against pulmonary fibrosis in the future.

Background: Arsenic is a potent environmental toxin with dangerous effects on human and animal populations. Heteroxenia fuscescens (H. fuscescens) extract exhibits potential health effects. The purpose of this study was to assess the protective effect of H. fuscescensextract against sodium arsenite-induced infertility and toxicity in rats. Methods: Forty male rats were separated into four groups as follows: control group (2% DMSO, orally), sodium arsenite (10 mg/kg, orally), sodium arsenite + H. fuscescens extract (60 mg/kg in 2% DMSO), and H. fuscescens extract (60 mg/kg in 2% DMSO). Results: GC/MS analysis of H. fuscescens indicates the presence of 10 compounds at retention times of 6.00, 12.53, 19.04, 24.60, 28.56, 35.66, 38.99, 45.29, 48.02, and 52.14. fuscescens extract improves levels of sperm count (53.33 ± 1.52), motility (43.00 ± 1.10), FSH ( 2.17 ± 0.04), LH (2.43 ± 0.06), testosterone (1.87 ± 0.02), and testis weight (0.49 ± 0.01). The antioxidant activity of H. fuscescens extract was reported by a significant decrease in MDA (1.02 ± 0.01) and NO (520.39 ± 14.99) levels, while it significantly increased levels of GSH (1.77 ± 0.07), and CAT (71.38 ± 3.45). Histopathological alterations of the testes, liver, and kidney observed with sodium arsenite have been improved in the treatment group. Conclusion: Heteroxenia fuscescens is beneficial in restoring male sex hormone levels, maintaining a healthy sperm profile, and reducing oxidative stress, all of which lead to an improvement in male rat fertility.

Bioactive peptides derived from soybeans have recently been identified as having potential health benefits for preventing and curing cancer and cardiovascular disorders. This narrative review focuses on the potential role of these peptides in such conditions and the possible mechanisms by which they may act. Soybean-derived bioactive peptides have been found to possess anti-tumor, antioxidant, anti-inflammatory, and cholesterol-lowering effects. Animal and in vitro studies have demonstrated that these peptides can modulate multiple signaling pathways, including those involved in the regulation of apoptosis, angiogenesis, and cell proliferation. Furthermore, they may protect against oxidative stress and lipid accumulation, which are associated with cancer and cardiovascular diseases. Also, soybean peptides have been shown to stop enzymes from breaking down cancer-causing chemicals and reduce the production of pro-inflammatory cytokines, which are linked to a higher risk of heart disease. The potential of soybean-derived peptides as a therapeutic tool in cancer and cardiovascular diseases is promising. However, further studies are needed to elucidate their mechanisms of action and assess their safety and efficacy in clinical settings.

Aims: The study aimed to search of new molecular complexes of licorice saponin with fluoroquinolone antibiotics and to explore their pharmaceutical potential. Background: Molecular complexation of triterpene glycosides with pharmaceutical substances reduces side effects and therapeutic doses, increases bioavailability and stability, and expands the spectrum of biological activity of drugs. Glycyrrhizic acid is the major triterpene glycoside of licorice. Molecular complexes of monoammonium salt of glycyrrhizic acid (glycyram, GC) with fluoroquinolone antibiotics have not been described. Objectives: This study is devoted to the preparation and analysis of molecular complexes of GC with fluoroquinolones, and investigation of their antimicrobial activity. Methods: Complexation was studied via FT-IR spectroscopy, UV-Vis spectroscopy and mass spectrometry methods. Results: Molecular complexes of GC with fluoroquinolone antibiotics, along with their benzylated derivatives, were obtained for the first time. Conclusion: The complexes composition was defined as 1:1. Intermolecular hydrogen bonds are formed during complexation. In addition, stability constants of 10⁵ Ц#156;^-1 order were calculated. Some complexes are comparable in antimicrobial activity with individual antibiotics ciprofloxacin (CP) and moxifloxacin (Moc) or surpass them in relation to a number of bacteria. These molecular complexes could be potential low-dose drugs with antimicrobial activity.