International Journal of Pharmaceutical Sciences and Drug Research

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https://imsear.searo.who.int/handle/123456789/234707

Editor: Dr. Kalpesh Gaur

ISSN: 0975-248X

Frequency: Quarterly

Language: English

Open Access Peer-reviewed journal

Web site: https://ijpsdr.com/index.htm

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Now showing 1 - 20 of 282

Molecular Docking Studies to Identify Inhibitors of Norepinephrine Reuptake from Marine Algae
(MRI Publication Pvt. Ltd., 2023-12) Razvi, Ummehani A.; Kamble, Laxmikant H.
Depression is one of the major mental health problems at prevalence now days. It can be characterized by poor concentration, low self-esteem, losing interest in family or social life, feeling tired or fatigue, suicidal thoughts and similar symptoms. There are treatments like psychotherapies, antidepressants and electroconvulsive therapies available, but there is need to identify more effective treatment with lesser side effects. Marine organisms like algae, sponges or corals are been investigated to explore their potential as antidepressants. This article aims to explore the potential of some compounds from marine algae by molecular docking and assessment of pharmacokinetics. Human norepinephrine transporter (hNET) was used as target for this study as this transporter is responsible to reuptake norepinephrine and disturbs chemical balance of brain, which can be a cause for depression. Binding affinity of these compounds was compared with binding affinity of prescribed drug levomilnacipran. From 14 selected compounds, 13 showed higher binding affinity towards hNET. Among all compounds, saringosterone has highest binding score. Pharmacokinetics properties were constructive for most compounds. Compounds showed weaker druglikeness and drugs score but can be optimized to enhance it. Compounds identified as inhibitors of NET can be developed as drug molecules in future or algal source for it can be taken as a food supplement.
Design and Development of Some Pyrimidine Analogues as an Anthelmintic Agent
(MRI Publication Pvt. Ltd., 2024-02) Pawar, Smita J.; Dorugade, Rahul; Kale, Amol P.; Zope, Dhanashri
Anthelmintic drugs are used to treat parasitic infections and acknowledge the challenge in developing effective anthelmintics due to the significant homology between parasites and their hosts. Despite the existence of various anthelmintic drugs in the market, the emergence of drug resistance necessitates the continuous development of new and more efficient drugs to combat parasitic infections. The development of anthelmintic drugs involves a multi-faceted process that aims to create effective treatments against parasitic infections. Pyrimidines have been investigated for their potential anthelmintic activity. Therefore, the present study involves the synthesis of derivatives based on pyrimidine. The series of 4-amino-2-hydroxy-6-substituted phenyl pyrimidine-5-carbonitrile was synthesized by treating substituted benzaldehyde with malononitrile and urea. The synthesized compounds were subsequently screened for their anthelmintic efficacy. The chemical structures were confirmed by infrared (IR) and proton nuclear magnetic resonance (1H-NMR) spectroscopy. The anthelmintic activity was performed on the adult Indian earthworm Pheretima posthuma. In-vitro anthelmintic studies revealed that, among all the screened compounds, compound 1f demonstrated significant or appreciable anthelmintic properties. Molecular docking was conducted on quinol-fumarate reductase to elucidate potential interactions between the newly synthesized pyrimidine derivatives and the specific cavity of the quinol-fumarate reductase enzyme. This analysis aimed to gain insights into the binding interactions and the possible mechanism of action of the synthesized compounds.
Identification of Serotonin Transporter Inhibitors from Selected Marine Alkaloids: A Molecular Docking and ADME Study
(MRI Publication Pvt. Ltd., 2023-12) Razvi, Ummehani A.; Kamble, Laxmikant H.
One of the common mental illnesses that affect people worldwide is depression. It can impact people from all backgrounds and age groups. Despite having medications for depression very few people respond to it in efficient manner. Currently used antidepressants show side effects like urine retention, nausea, weight gain, cardiovascular disorders, etc. To eradicate these side effects natural compounds are being evaluated for their therapeutic potentials. Metabolites obtained from marine organisms possess diverse beneficial effects. Wide variety of sponges, corals, seaweeds contains compounds with magical properties to heal mental disorders. This study demonstrates molecular docking of serotonin transporter (SERT) with some marine alkaloids. Results generated from PyRx virtual screening software shows that out of thirteen selected alkaloids only Gelliusine A have higher binding affinity than prescribed antidepressant Paroxetine. According to SwissADME, most of the selected alkaloids showed better Absorption, Distribution, Metabolism and Excretion (ADME) properties. But Gelliusine A has low gastrointestinal absorption and does not cross Blood Brain Barrier (BBB). Further optimization and experimental investigations of these compounds are needed to enhance their properties to become better antidepressants against reuptake of serotonin.
Combined Antidepressant Effect of Acetyl-L-Carnitine and Bupropion against Experimental Animal Model
(MRI Publication Pvt. Ltd., 2024-02) Padhy, Jagamohan; Samal, Pradeep Kumar; Choudhary, Rajesh; Shree, Jaya; Vaishnaw, Bharti
Depression is one of the most common mental diseases characterized by mood disorders affecting around 322 million individuals in the world. Depression is a feeling of inadequacy, dejection, anhedonia, and decreased activity in any action. Previously acetyl-L-carnitine reported beneficial effects on lipid metabolism, neuroprotection, and some types of depression. Therefore, in the present study, we evaluated the combined effect of acetyl-L-carnitine and bupropion against experimental-induced depression. Albino rats were divided into different groups (each group contained six animals). Normal groups received saline (1 mL/kg, i.p.). The standard group received imipramine (20 mg/kg, i.p.). The ALC group received acetyl-L-carnitine (100 mg/kg, i.p.), and the BPR group received bupropion (20 mg/kg, i.p.). T I and T II groups received acetyl-L-carnitine (30 mg/kg, i.p.) + Bupropion (10 mg/kg, i.p.) and acetyl-L-carnitine (80 mg/kg, i.p.) + Bupropion (30 mg/kg, i.p.), respectively. Antidepressant effects were assessed by forced swim test and sucrose preference test. In both models, the combined effect of the drug produced a significant (p < 0.05) antidepressant action as compared to the depression control group. Based on the findings, the combined effect of acetyl-L-carnitine and bupropion had a better therapeutic effect to combat depression as compared to individual treatments.
Role of Bougainvillea glabra Stem Extract on Paracetamol and Alcohol-Induced Hepatotoxicity in Rats
(MRI Publication Pvt. Ltd., 2024-02) Manjunath, Lakshminarayana; Jogpal, Vikas
The current study investigates the in-vivo hepatoprotective effectiveness of Bougainvillea glabra stem extract against alcohol and paracetamol-induced hepatotoxicity in animal models. The alterations in liver enzymes including serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP), and total bilirubin are studied in rats given B. glabra extract with paracetamol or alcohol to produce hepatotoxicity. The levels of glutathione and lipid peroxidation were also examined, and the outcomes were contrasted with silymarin as the reference. The acute toxicity studies presented the plant extract under category 5 of GHS system, which further motivated the studies for hepatoprotective activity. The induction of hepatotoxicity was confirmed with the elevated levels of serum and tissue biochemical by the administration of paracetamol and alcohol. Under paracetamol as a hepatotoxin, the animals with 200 and 400 mg/kg p.o demonstrated near figures for SGPT and SGOT of the group treated with silymarin with significance. The results were still more appreciative under alcohol as a hepatotoxin. In both cases, the group with 400 mg/kg p.o gave a promising result with the reduced inflammatory cells under histopathological studies.
Expeditious Microwave-Assisted Synthesis of 1,3-Benzoxazoles Incorporating Substituted Thiazolidinone Moieties
(MRI Publication Pvt. Ltd., 2023-12) Piste, Pravina
The rapid synthesis of 3-[4-(1,3-benzoxazol-2-yl)phenyl]-2-aryl-1,3-thiazolidin-4-one 4(a-h) was achieved through microwave-assisted methods. This involved the reaction of Schiff bases derived from 2-(4-amino phenyl) benzoxazole 3(a-h) with ethanol, SHCH2COOH (thioglycolic acid) (1 mol, 0.92 mL), and ZnCl2 (5 mol%) under microwave irradiation (400W, 146°C) for 3-4 minutes, resulting in excellent yields. Compound precursors 3(a-h) were prepared from aromatic aldehydes and 2-(4-amino phenyl) benzoxazole in ethanol, followed by microwave irradiation for 1-2 minutes, with reaction progress monitored via TLC. The expeditious reaction time is a notable advantage of this protocol. Comprehensive structural elucidation of the synthesized compounds involved elemental analysis, IR, NMR, 13C NMR, and Mass spectroscopy. These newly synthesized compounds, 4(a-h), were subjected to in vitro antimicrobial screening against Staphylococcus aureus, Escherichia coli, and antifungal screening against Aspergillus Niger. The zone of inhibition in millimeters was measured using the cup plate method. Several compounds within the series exhibited substantial activity when compared to the standard drugs streptomycin and Fluconazole.
In-silico Studies of Heterocyclic Benzoxazole Derivatives as an Anticancer Agent: Molecular Docking, 2D and 3D QSAR
(MRI Publication Pvt. Ltd., 2023-12) Pawar, Smita J.; Zope, Dhanashri; Kale, Amol P.
In-silico molecular docking studies and QSAR study of benzoxazole derivatives synthesized by Kakkar et al. was done. Comparative studies of docking of 5-flurouracil and 20 compounds revealed presence of considerable interactions which indicates the affinity of newly synthesized compounds for thymidylate synthase. The statistically significant 2D-QSAR models were developed using molecular design suite (VLifeMDS 4.6). The study was performed with 20 compounds (data set) using sphere exclusion (SE) algorithm, random selection and manual selection methods used for the division of the data set into training and test set. Multiple linear regression [MLR] methodology with stepwise (SW) forward-backward variable selection method was used for building the QSAR models. The results of the 2D-QSAR models were further compared with 3D-QSAR models generated by kNN-MFA, (k-Nearest Neighbor Molecular Field Analysis) investigating the substitutional requirements for the favourable anticancer activity against HCT 116 cell line and providing useful information in the characterization and differentiation of their binding sites. The results derived may be useful for further designing of benzoxazole derivatives as anticancer agents prior to synthesis.
A Quantitative Approach for the Determination of Elemental Impurities in Zinc Orotate Dihydrate Drug Substance by ICP-MS Method
(MRI Publication Pvt. Ltd., 2023-12) B, Sivagami; G, Gurupriya; Raju, Chandasekar; M, Niranjan Babu
These days elemental impurities are commonly present in active pharmaceutical ingredients, raw materials, during synthesis of compounds, drug excipients, finished products, equipment, container and closures. ICPMS is one of the advanced techniques to analyse elemental impurities in drug substances. An ICP-MS method was developed and validated for testing 17 elements, namely, V, Co, Ni, As, Se, Ru, Rh, Pd, Ag, Cd, Os, Ir, Pt, Au, Hg, Tl and Pb in zinc orotate dihydrate. The samples were analysed after diluting with concentrated nitric acid and concentrated hydrochloric acid. Li, Y, Tl, Co & Ce were assigned tuning solution to correct the baseline drift and matrix interference. The RF power was 1550 W, RF matching was 1.80 V, sample depth was 8.0 mm, nebulizer gas flow was 1.01 L/min, nebulizer pump flow was 0.10 rps, spray chamber temperature 2o C, He flow rate was 4.3 ml/min and the energy discrimination rate was 3.0 V. All 17 elements exhibited excellent linearity in their testing range, with a coefficient of determination???0.9996. The limits of detection of the 17 elements were within the range of 0.0004–0.00411ppm. The intra- and inter-day precision (relative standard deviation) was?
Development and Validation of The Menstrual Health Outcome Questionnaire to evaluate quality of life among women during menstrual cycle
(MRI Publication Pvt. Ltd., 2023-12) Parmar, Priyanka R.; Deshpande, Shrikalp S.
Menstruation is a physiological process experienced by adolescent girls and women. Menstruation and premenstrual symptoms affect the Quality of Life. Different scales are available to measure QOL for different gynaecological problems but none scale available to measure QOL during Menstruation. WHO defines Quality of Life as an individual's perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns. It is a multidimensional concept that includes domains related to physical, mental, emotional and social functioning. It goes beyond direct measure of population health, life expectancy and causes of death and focuses on the impact health status on quality of life. To develop a comprehensive instrument to assess the health-related QOL among the women during menstruation. The creation of a scale to assess QOL during the menstrual cycle is indeed a significant endeavour. Menstrual Health Outcomes Questionnaire contains 35 questions from different domains. After getting ethical approval pilot and pivotal study conducted. Adolescents were randomly recruited in the study. Data was captured and entered in SPSS version 20. Principle factor analysis was determined to find construct validity among independent and dependent variables. Man-Whitney U test was determined. Questionnaire has Cronbach’s alpha 0.796, determined 35 questions. Intraclass corelation coefficient was found 0.786. KMO and Bartlett’s test was found 0.820 with high significance. (p=0.000) Menstrual Health Outcome Questionnaire has been established as a valid and reliable tool for assessing the QOL among women during menstruation.
Evaluation of Anti-Urolithiatic activity of Bougainvillea spectabilis Wild. Against Sodium Oxalate-Induced nephrolithiasis in rats
(MRI Publication Pvt. Ltd., 2023-02) Das, Prabhat K.; Vaghela, Jai S.
As there is no effective treatment for kidney stones, the development and progression of renal calculi continue to be a cause for concern despite developments in contemporary medicine. In the current study, the anti-urolithiasis activity of Bougainvillea spectabilis Willd. against sodium oxalate (NaOx)-induced urolithiasis in rats was studied. Leaves of B. spectabilis were extracted with various solvents, i.e., petroleum ether, chloroform, ethyl acetate, ethanol, and water. Albino wistar male rats were divided into five groups of six animals each. All groups except the positive control were treated intraperitoneally with sodium oxalate (70 mg/kg) for 10 days. Treatment with the standard drug cystone (5 mL/kg), ethanol, and aqueous extracts (200 mg/kg) was given to the respective groups for 10 days of study. On the 10th day, serum creatinine, calcium, uric acid, blood urea nitrogen, urine calcium, oxalate, and uric acid levels were estimated, along with urine microscopy to confirm crystals. Kidneys were isolated and used for histopathological studies. The results suggested that the administration of B. spectabilis to rats with sodium oxalate-induced lithiasis reduced and prevented the formation of urinary stones. Also, the treatment of lithiasis-induced rats with the toxic control drug and extracts of B. spectabilis restored all the elevated urine and serum biochemical parameters, including creatinine, calcium, oxalate, uric acid, and blood urea nitrogen, and significantly increased the urine volume. The histopathology showed depositions of a large number of calcium oxalate crystals in the kidney in the calculi-induced group with enlargement of glomeruli and necrosis of tubules, while in the standard and extract-treated groups, small and fewer deposits were seen with the recovered architecture of the kidney tubules. The result indicates the anti-urolithiasis activity of B. spectabilis mediated possibly by the presence of flavonoids, calcium oxalate crystal inhibitors, and antioxidant properties which maintain the balance between stone promoters and inhibitors constituents and this study rationalized its medicinal use in urolithiasis.
Isolation, Characterization, In-silico and enzyme Inhibition studies of plant Bougainvillea spectabilis against a hyperoxaluria Initiator Glycolate oxidase
(MRI Publication Pvt. Ltd., 2023-12) Das, Prabhat K.; Vaghela, Jai S.; Deshmukh, Nitin
Glycolate oxidase has long been thought to be a key player in the formation of oxalate accumulation in the human body. Both the endogenous synthesis of oxalate and clinically identified targets for the therapy of primary hyperoxaluria are affected by this disorder. The role of glycolate oxidase has been investigated in order to provide additional insight into the possible molecular pathways involved. The presence of flavonoids in the ethanolic extract led to the conclusion that it was suitable following phytochemical screening. Column chromatography was used to isolate the active component using the proper solvent system. The structure of the active, separated phytoconstituents was ascertained using a variety of spectral techniques, including FTIR, NMR, and GCMS analysis. Following structure elucidation, glycolate oxidase (PDB: 2RDT) and Quercetin were used as standards in molecular docking investigations. Studies on in- vitro enzyme inhibition were carried out to verify the outcome. Following the investigation of the isolated compound's spectral data, it was determined that the structure might be 4-hydroxy-3-nitro coumarin. Using conventional standard flavonoid Quercetin, additional molecular docking studies were carried out to speculate on the compound's potential mechanism of action. The chemical was discovered to be effective during the inhibition of the target enzyme by occupying the majority of the amino acid active sites. In-vitro enzyme inhibition tests provided additional confirmation for the computational investigations. The isolated compound's significant IC50 value in this study was demonstrated in comparison to standard Quercetin's efficacy. These findings supported the isolated compound's potential mechanism of action, which involves inhibiting the enzyme glycolate oxidase, in terms of its anti-urolithiasis efficacy. The study also provided justification for the compound's potential therapeutic application in urolithiasis.
STUDIES ON FIXED DOSE COMBINATION OF IBRUTINIB AND QUERCETIN SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEMS IN HUMAN CANCER CELL LINES
(MRI Publication Pvt. Ltd., 2023-12) Bagri, Rashmi; Ravouru, Nagaraju
Ibrutinib (IB), irreversibly inhibits Bruton’s Tyrosine Kinase which plays a crucial role in the tumor microenvironment and Quercetin (QC) shown apoptosis induction, angiogenesis inhibition, and anti-proliferative action against several human carcinoma cells. The self nano-emulsifying drug delivery system (SNEDDS) is suitable for the loading of insolubilized oil-based compounds such as Ibrutinib and Quercetin. In the current study IB with QC was formulated into SNEDDS and cytotoxicity was determined by using Human malignant melanoma (A-375) and Human lung adenocarcinoma (A549) cell lines. The optimized loaded formula consisted of Castor oil, Kolliphor® RH 40, and PEG-600. The optimized formulation was evaluated for physical parameters and the results were satisfactory. For cytotoxicity studies MTT assay was conducted for these combinations, IC50 values were calculated for the tested compound. In A-549 adenocarcinoma cell line, the calculated IC50 values (?M) for the test compounds T1 (pure IB+QC) and T2 (IB+QC SNEDDS) were 70.34+ 0.8 µM and 85.46 + 0.93 µM at 24?h study, respectively. In A-375 cancer cell line, IC50 values for the compounds T1 and T2 were 59.52 + 0.87 µM and 88.43 + 1.03 µM for 24?h study, respectively. It was observed that the IC50 of IB-QC loaded SNEDDS was higher than pure drug combination and these enter the cells by active transport and induce cytotoxicity to the cells. The overall results from the studies suggest that IB-QC-loaded SNEDD provided synergistic effects, which could play a significant role in the percentage of cell death.
In-silico Design of Potent Anti-Tubercular Agents Containing Isatinylthiosemicarbazone Pharmacophore
(MRI Publication Pvt. Ltd., 2023-12) Raut, Kunal G.; Kothawade, Sachin N.; Pande, Vishal V.; Wagh, Vaibhav S.; Bole, Sandesh S.; Sumbe, Rajashri B.
A recent study reveals that Isatinylthiosemicarbazone analogues inhibit mycobacterial growth by inhibiting the Isocitrate Lyase (ICL). Hence Two-dimensional (2D), Three-dimensional (3D), and Group QSAR (GQSAR) studies were performed to reduce the amount of pharmacophore needed to make effective ICL inhibitors. New Chemical Entities (NCEs) were created based on the findings of all QSAR studies. It was discovered that QSAR models produced noticeably positive statistical findings. i.e. (r2 > 0.7), cross-validation (q2 > 0.6), and external validation (pred_r2 > 0.6), indicating high predictability of all models. Utilizing molecular docking studies, the binding affinities of designed NCEs were investigated for the ICL enzyme (PDB code: 1F8M). The absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of designed NCEs were expected to have a pharmacokinetic profile similar to their drug. Overall, it is important to state that the methodology used for pharmacophore optimization using 2D, 3D, G-QSAR, and Molecular Docking ADMET research works was discovered to be extremely accurate.
Detection of 3-4 Methylenedioxyamphetamine from Drug Abuser’s Fingers and Toenails using Liquid Chromatography with Mass Spectroscopy
(MRI Publication Pvt. Ltd., 2023-12) Bansod, Nandini; Goutam, M.P.
Nails can stably accumulate substances for extended periods of time, thus providing retrospective information regarding drug abuse and pharmaceutical use. In recent years, drug analysis in human nail clippings has proven its significant value in forensic toxicological applications, identification of in utero drug exposure, monitoring of drug treatment programmes, and therapeutic drug monitoring. Nails have various advantages over conventional matrices (blood and urine), which include a longer detection window (months to years), non-invasive sample collection, and easy storage and transportation. These aspects make nails a very significant matrix for forensic toxicology and therapeutic drug monitoring. Because of the low concentrations of drugs of abuse and pharmaceuticals present in nails and the complexity of the keratinized matrix, analytical techniques need to be more sensitive, and sample preparation is crucial. The aim of the present study is to develop a simple high-performance liquid chromatography-mass spectroscopy method for the identification and quantitation of 3,4-methylenedioxyamphetamine (MDA) in fingernail and toenail clippings. Finger and toenail clippings were collected from six users undergoing treatment at a rehab centre in Ujjain, M.P., India. Nail clippings were initially decontaminated, then hydrolyzed in 1 M NaOH at 370°C, extracted with ethyl acetate, diluted with methanol, and then subjected to LC-MS analysis. The calibration curve was constructed over the concentration range of 0.5 ng/mL to 30 ng/mL using the MDA reference standard. The limit of detection was calculated at 1.10 ng/mL and the limit of quantification recorded at 3.67 ng/mL in standard solutions, whereas the respective values in spiked nail clippings were 1.21 ng/mg and 4.6 ng/mg. Through the developed method, significant results have been obtained in original nail clippings with mean concentration ranges of 0.12 ng/mg in fingernails and 0.08 ng/mg in toenails in six abuser samples. The new method developed has been found to be capable of detecting the 3,4-methylendioxyamphetamine (MDA) drug in nail clippings even after 90 days of drug intake.
Formulation Development and Evaluation Studies of Linezolid Inhaler in the Treatment of Tuberculosis
(MRI Publication Pvt. Ltd., 2023-12) Borkar, Gauri; Chemate, Satyam
The primary objective of this study was to prepare and evaluate a linezolid inhaler. Dry powder inhaler liposomes were formulated to investigate the efficacy of pulmonary delivery of Linezolid for tuberculosis. The liposomes were prepared using soya lecithin and cholesterol in different weight ratios, drug in a constant amount, and two different methods: physical dispersion and ethanol injection. The F9 formulation was characterized for physical and chemical properties such as vesicle size, shape, and zeta potential. The results of physical characterization, in vitro testing, and stability studies indicate that liposomes containing Linezolid can be used for the treatment of tuberculosis. The evaluated batch exhibited favorable physicochemical properties, with spherical liposomes having a mean size below 100?nm and high entrapment efficiency (98.8%). The prepared liposomal dry powder inhalers (DPIs) sustained drug release for up to 8 hours. Liposome stability was assessed 90 days after storage at room temperature, revealing its stability. The liposomal formulation had steady zeta potential, good entrapment efficiency, improved stability, and an extended drug release time. In conclusion, linezolid-loaded liposomal inhalers were successfully formulated.
DESIGN AND COMPUTATIONAL EVALUATION OF NEW CARBAMATE DERIVATIVES FOR THE INHIBITION OF MONOACYLGLYCEROL LIPASE ENZYME BY USING DOCKING
(MRI Publication Pvt. Ltd., 2023-10) Kashyap, Abhishek; Rani, Dimpy; Kumar, Suresh; Bhatt, Shailendra
Different disorders and physiological process have been found to be associated with monoacylglycerol lipase enzyme in humans, like pain, inflammation, and neurodegenerative diseases also. The enzyme is a 33 KDa in weight and a type of serine hydrolase enzyme in nature. The presence of enzyme has been reported in both central and peripheral nervous systems and has show its importance as a key signalling factor in endocannabinoid signalling network system. The enzyme has also reported as source of free fatty acid provider for the cancer cell and tumour growth and their proliferation. In proliferative cancer cells, increased the monoacylglycerol lipase activity is observed. The growth, migration and survival of cancer cells have also found to be associated with phosphatidic acid, lysophosphatidic acid, sphingosine phosphate and prostaglandin E2, which are act as signalling molecules and are found to be derived from free fatty acid. These are also found to be related to the growth, transmission and viability of cancer cells, which increases with the enzyme activity. In the present study we performing computation screening studies of newly designed monoacylglycerol inhibitors which contains carbamate features, these molecules are designed based on previously developed monoacylglycerol carbamate inhibitors.
In silico studies of quinazolinone analogues to distinguish their hypothetical binding mode using the X-ray crystal structure human carbon anhydrase II (HCAII) enzyme complex with sugar sulfamate for anticonvulsant activity
(MRI Publication Pvt. Ltd., 2023-10) Amrutkar, Rakesh D.; Ranawat, Mahendra Singh
The quinazolinone moiety is a significant pharmacophore depicts various types of pharmacological activities as shown in recent exhaustive ligatures serve. Quinazolinone exhibit potent central nervous system (CNS) activities like anti-anxiety, analgesic, anti-inflammatory and anticonvulsant. To develop these views and application profiles, attempt have been made to report a drug/ligand or receptor/protein interactions by identifying the suitable active site against X-ray crystal structure of Human Carbonic Anhydrase II (HCA II) enzyme for anticonvulsant activity using Vlife MDS version 4.6 Software because the protein-ligand interaction plays a significant role in structural based drug designing. The interaction was evaluated based on the score comparison between quinazolinone derivatives with sugar sulfamate. The quinazolinone ring forms hydrophobic and hydrogen bond contacts amino acid residues. The ligands 4t and 4s were shown to possess minimum dock score i.e. minimum binding energy in Kcal/mole i.e. these molecules has more affinity for active site of receptor. Clearly, Molecules having low dock score and binding energy shows more affinity towards the receptor. The data reported in this article may be helpful for the medicinal chemists who are working in this area.
Synthesis, antimicrobial activity and Molecular docking study of some novel isoxazole incorporated benzimidazole derivatives
(MRI Publication Pvt. Ltd., 2023-12) Sharma, Pankaj Kumar; Sharma, Chandra Shekhar
A series of novel isoxazole-incorporated benzimidazole derivatives was synthesized and investigated for antimicrobial activity. The structures of all synthesized compounds were confirmed by means of elemental analysis, infrared spectroscopy (IR), proton nuclear magnetic resonance (1H-NMR), and liquid chromatography-mass spectrometry (LC-MS). All compounds were evaluated for antimicrobial activity cup plate method against Staphylococcus aureus, Bacillus anthracis, Pseudomonas aeruginosa, Escherchia coli, Candida albicans and Aspegillus niger. The 4d, 4f and 4j compounds showed significant activity against gram-positive and gram-negative bacteria. On the basis of the interaction energy criterion, compound 4f showed the best docking interactions equal to 7.0 kcal/mol.
Development and optimization of enzalutamide nanosuspension by design of experiments for dissolution enhancement
(MRI Publication Pvt. Ltd., 2023-12) Patel, Rajendra; Parmar, Komal
Enzalutamide is an anticancer molecule used for prostate cancer. The goal of the study was to develop a nanosuspension of enzalutamide in order to improve its solubility and dissolution properties. High speed homogenization method was employed to formulate the nanosuspension. Preliminary studies suggested amount of stabilizer, homogenization time and homogenization speed as critical variables to be taken for the optimization process. Box-Behnken design was employed for the optimization of process and formulation variables. Nanosuspension was evaluated for particle size, PDI, zeta potential, and in vitro drug release at 10 min (D10) studies. Regression analysis suggested the influence of independent variables on the responses. The optimized batch obtained from overlay plot exhibited 198.36 nm of particle size, (-33.27 mV of zeta potential and 80.47 % of D10 values. The characterization studies i.e. DSC, and XRD illustrated retention in crystallinity of drug. The drug and formulation were found to be stable over a 6-month period in accelerated stability testing. Using high speed homogenization method, particle size of the formulation was reduced to nano-size which was further responsible for the improvement in dissolution and bioavailability of drug.
GC-MS Analysis and In Silico Docking Study of Active Antifungal Components of Entada rheedei Spreng. (Seeds)
(MRI Publication Pvt. Ltd., 2023-12) Belho, Neithongunuo Angela; Veswuh, Rukutalu; Solo, Peter
Entada rheedei Spreng., is a liana or a climber belonging to the family Fabaceae and is widely distributed in tropical and sub-tropical areas. The seeds of Entada rheedei Spreng. has been found to contain important phytoconstituents such as phenolics, thioamides and saponins. In this study, we investigated the antifungal properties of Entada rheedei Spreng. and imply in silico methods to study its bio-active phytoconstituents. The aqueous extract of the seeds exhibited significant antifungal inhibitions against Aspergillus flavus and Aspergillus fumigatus. GC-MS analysis reveals the presence of 13 bioactive compounds that could be potent fungal inhibitors. Subsequently, in silico Molecular docking analysis recognised benzoic acid, 2, 4-bis (trimethylsilyloxy)- trimethylsilyl ester as the active antifungal constituent of the aqueous extract with a docking score of -8.0570 and -9.4564 kcal/mol against Aspergillus flavus and Aspergillus fumigatus respectively. The insilico studies were further backed by 100 ns Molecular Dynamics simulation studies. This study can thus lead to the production of potent plant based antifungal drugs.

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