Self-micellizing solid dispersion of thymoquinone with enhanced biopharmaceutical and nephroprotective effects.

The present study was designed to develop a self-micellizing solid dispersion (SMSD) containing Thymoquinone (TQM), a phytonutrient obtained from Nigella sativa seeds, aiming to improve its biopharmaceutical and nephroprotective functions. The apparent solubility of TQM in polymer solutions was used to choose an appropriate amphiphilic polymer that could be used to make an SMSD system. Based on the apparent solubility, Soluplus® was selected as an appropriate carrier, and mixing with TQM, SMSD-TQM with different loadings of TQM (5-15%) was made by solvent evaporation and freeze-drying techniques, respectively, and the formulations were optimized. The optimized SMSD-TQM was evaluated in terms of particle size distribution, morphology, release characteristics, pharmacokinetic behavior, and nephroprotective effects in a rat model of acute kidney injury. SMSD-TQM significantly improved the dissolution characteristics (97.8%) of TQM in water within 60 min. Oral administration of SMSD-TQM in rats exhibited a 4.9-fold higher systemic exposure than crystalline TQM. In a cisplatin-induced (6 mg/kg, i.p.) acute kidney-damaged rat model, oral SMSD-TQM (10 mg/kg) improved the nephroprotective effects of TQM based on the results of kidney biomarkers and histological abnormalities. These findings suggest that SMSD-TQM might be efficacious in enhancing the nephroprotective effect of TQM by overcoming biopharmaceutical limitations.

Synthesis of Sugar and Nucleoside Analogs and Evaluation of Their Anticancer and Analgesic Potentials.

Chemical modification of sugars and nucleosides has a long history of producing compounds with improved selectivity and efficacy. In this study, several modified sugars (2-3) and ribonucleoside analogs (4-8) have been synthesized from α-d-glucose in a total of 21 steps. The compounds were tested for peripheral anti-nociceptive characteristics in the acetic acid-induced writhing assay in mice, where compounds 2, 7, and 8 showed a significant reduction in the number of writhes by 56%, 62%, and 63%, respectively. The compounds were also tested for their cytotoxic potential against human HeLa cell line via trypan blue dye exclusion test followed by cell counting kit-8 (CCK-8) assay. Compound 6 demonstrated significant cytotoxic activity with an IC50 value of 54 µg/mL. Molecular docking simulations revealed that compounds 2, 7, and 8 had a comparable binding affinity to cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. Additionally, the bridged nucleoside analogs 7 and 8 potently inhibited adenosine kinase enzyme as well, which indicates an alternate mechanistic pathway behind their anti-nociceptive action. Cytotoxic compound 6 demonstrated strong docking with cancer drug targets human cytidine deaminase, proto-oncogene tyrosine-protein kinase Src, human thymidine kinase 1, human thymidylate synthase, and human adenosine deaminase 2. This is the first ever reporting of the synthesis and analgesic property of compound 8 and the cytotoxic potential of compound 6.

Safety and efficacy of favipiravir for the management of COVID-19 patients: A preliminary randomized control trial.

Background: The novel coronavirus disease, commonly called COVID-19, has already killed millions of lives. Our study aimed to identify a safe and right drug for the management of such globally threatened COVID-19. Methods: This preliminary double-blinded randomized controlled trial was done among 57 hospitalized COVID-19 patients in the early stage of their illness. Of them, 29 patients received Favipiravir (FVP) and the remaining 28 patients received a placebo under the standard of care. Among the patients, 4 from Favipiravir (FVP) group and 3 from the placebo group were discontinued. The patients were observed regularly for a period of 10 days. Result: In our study, the FVP treated group showed accelerated viral clearance compared to the placebo-treated group. Assessment of chest X-ray showed remarkable improvement of pheumonia patient in group A compared to Group B. Hematological and Biochemical parameters such as total WBC count, neutrophil and lymphocyte counts were examined. No significant differences in the hematological parameters such as WBC count, neutrophil and lymphocyte counts in Group A and Group B patients. Liver transaminases levels were also stable in FVP treated group (average ALT ranges 39.4-46.2; AST 28.2-32.8). Conclusion: The drug Favipiravir displayed remarkable improvements in the clinical conditions and recovery of COVID-19 patients at the early stages of their infections.

Synthesis, characterization and in vitro, in vivo, in silico biological evaluations of substituted benzimidazole derivatives.

A series of substituted benzimidazole derivatives were synthesized by reacting O-phenylenediamine with various aromatic aldehydes or glycolic acid using various inexpensive reagents in aqueous media. Synthesized compounds were characterized and elucidated by IR, 1H NMR, ESI-MS spectra. Resultant compounds were screened for in vitro antimicrobial, cytotoxic, antioxidant, lipid peroxidation and cholinesterase inhibitory activities, in vivo analgesic and anti-inflammatory, and in silico anti-acetylcholinesterase and anti-butyrylcholinesterase activities. Among the synthesized compounds, compound 3b showed most promising central analgesic effect (46.15%) compared to morphine (48.08%), whereas compounds 6, 3c and 3a showed significant peripheral analgesic activity at two different dose levels (25 mg/kg and 50 mg/kg). Compounds 3b and 3a at the dose of 100 mg/kg showed significant anti-inflammatory effects from the first hour and onward, whereas compounds 6 and 3b showed moderate cytotoxic activities. In addition, compound 3a showed significant antioxidant activity having IC50 value of 16.73 µg/ml compared to 14.44 µg/ml for the standard BHT. Compound 6, 3a and 3b exhibited mild to moderate cholinesterase inhibitory activity. In silico studies revealed that compound 3a and 3b might be suitable for cholinesterase inhibitory activity. A comprehensive computational and experimental data suggested compounds 3b and 3a as the best possible candidates for pharmacological activity. All the experimental data were statistically significant (p < 0.01 level).

Status of psychological health of students following the extended university closure in Bangladesh: Results from a web-based cross-sectional study.

Students' severe affective mental distress has emerged as significant public health attention globally because of the disastrous effects of coronavirus disease 2019 (COVID-19). The current study aimed at exploring the prevalence of two alarming psychological distresses, depression and anxiety, among university students following a prolonged shutdown of educational institutions in Bangladesh. A cross-sectional online-based study was conducted by deploying two standard scales to assess the depression and anxiety among Bangladeshi students from various universities amid the 2nd stream of the COVID-19 pandemic. A total of 568 Bangladeshi university students participated in this questionnaire-based survey through various social media platforms. Frequency and percentage distribution as univariate, chi-square (χ2) test as bivariate, and logistic regression as multivariate analyses were applied to investigate the prevalence of depression and anxiety and their associated various sociodemographic factors. After cleaning and eliminating the partial data, we analyzed 465 responses, where 42% were female and 64.3% were from public universities. Both mental disorders were prevalent in more than 50% of Bangladeshi university students. The students from the private universities were two times and 2.7 times more depressed and anxious, respectively than the students from the public universities. In addition, the students who became incomeless had significantly more anxiety (adjusted odds ratio [AOR] = 1.711; p = 0.018) than those who did not lose income source during the COVID-19 lockdown. The present study revealed that more than 50% of Bangladeshi university students were suffering from depression and anxiety. Several effective measures must be assured by the concerted efforts of university authorities, educationalists, and the Government to alleviate these distressing mental health burdens.

Isolation of phytochemical constituents from Stevia rebaudiana (Bert.) and evaluation of their anticancer, antimicrobial and antioxidant properties via in vitro and in silico approaches.

The current study was designed to isolate and characterize some bioactive secondary metabolites by using repeated chromatographic and spectroscopic techniques, targeting their anticancer, antimicrobial, and antioxidant properties through in vitro and in silico approaches. Six compounds were isolated and analyzed by thin layer chromatographic technique and the compounds were identified as 5-O-caffeoyl quinic acid (1), syringin (2), luteolin (3), apigenin (4), jhanol (5), and jhanidiol (6) based on spectroscopic methods. The cytotoxic effect of each compound was dose-dependent, and compound 1 showed a higher anti-proliferative effect (IC50 = 181.3 µg/ml) than other compounds (compound 2, 4, 5, and 6). Besides, compound 1 showed the most promising antibacterial activity with a zone of inhibition ranges from 12-15 mm against different strains compared to ciprofloxacin (14-22 mm). In contrast, compound 3 exerted the highest scavenging property against DPPH free radical. Finally, the in vitro bioactivities were also supported by molecular docking studies. The computational study demonstrated that the isolated compounds exerted stronger affinity compared to the standard drugs towards the binding sites of dihydrofolate reductase (DHFR), glutathione reductase, and urase oxidase.

A Comprehensive Account on Recent Progress in Pharmacological Activities of Benzimidazole Derivatives.

Nowadays, nitrogenous heterocyclic molecules have attracted a great deal of interest among medicinal chemists. Among these potential heterocyclic drugs, benzimidazole scaffolds are considerably prevalent. Due to their isostructural pharmacophore of naturally occurring active biomolecules, benzimidazole derivatives have significant importance as chemotherapeutic agents in diverse clinical conditions. Researchers have synthesized plenty of benzimidazole derivatives in the last decades, amidst a large share of these compounds exerted excellent bioactivity against many ailments with outstanding bioavailability, safety, and stability profiles. In this comprehensive review, we have summarized the bioactivity of the benzimidazole derivatives reported in recent literature (2012-2021) with their available structure-activity relationship. Compounds bearing benzimidazole nucleus possess broad-spectrum pharmacological properties ranging from common antibacterial effects to the world's most virulent diseases. Several promising therapeutic candidates are undergoing human trials, and some of these are going to be approved for clinical use. However, notable challenges, such as drug resistance, costly and tedious synthetic methods, little structural information of receptors, lack of advanced software, and so on, are still viable to be overcome for further research.

Synthesis, in vivo and in silico analgesic and anti-inflammatory studies of α-D-ribofuranose derivatives.

Five α-D-ribofuranose analogues (2, 3, 4, 5 and 6) were synthesized in good yields from 3-O-benzyl-4-C-(hydroxymethyl)-1, 2-O-isopropylidene-α-D-ribofuranose (1). The synthesized compounds were then subjected to analgesic, anti-inflammatory, antimicrobial and antioxidant assays. Compound 3 demonstrated 79.74% (P < 0.001) writhing inhibition and highest reaction time of 2.55 ± 0.13 min (P < 0.001) after 30 min of oral administration in peripheral and central analgesic assay, respectively, at 50 mg/kg dose. Compound 2 and 6 exhibited significant anti-inflammatory activity at 100 mg/kg dose with paw edema inhibition of 91.15% (P < 0.001) and 95.13% (P < 0.001), respectively, in 4th hour. The synthesized analogues did not show notable antioxidant and antibacterial properties. Molecular docking study revealed higher binding affinity of -8.1 kcal/mol and -8.9 kcal/mol of compound 3 towards cyclooxygenase-1 and phospholipase A2, respectively, compared to -7.7 and -7.6 kcal/mol respectively for corresponding native ligands. Compound 2 demonstrated binding affinity of -9.1 kcal/mol towards interleukin-1 receptor-associated kinase-4 compared to -8.7 kcal/mol of the native ligand. The molecular properties related to drug likeness of compounds were found to be within acceptable range. Synthesized D-ribofuranose analogues demonstrated promising analgesic and anti-inflammatory activities and further development may lead to new potent analgesic and anti-inflammatory agents.

Therapeutic Effectiveness and Safety of Repurposing Drugs for the Treatment of COVID-19: Position Standing in 2021.

COVID-19, transmitted by SARS-CoV-2, is one of the most serious pandemic situations in the history of mankind, and has already infected a huge population across the globe. This horrendously contagious viral outbreak was first identified in China and within a very short time it affected the world's health, transport, economic, and academic sectors. Despite the recent approval of a few anti-COVID-19 vaccines, their unavailability and insufficiency along with the lack of other potential therapeutic options are continuing to worsen the situation, with valuable lives continuing to be lost. In this situation, researchers across the globe are focusing on repurposing prospective drugs and prophylaxis such as favipiravir, remdesivir, chloroquine, hydroxychloroquine, ivermectin, lopinavir-ritonavir, azithromycin, doxycycline, ACEIs/ARBs, rivaroxaban, and protease inhibitors, which were preliminarily based on in vitro and in vivo pharmacological and toxicological study reports followed by clinical applications. Based on available preliminary data derived from limited clinical trials, the US National Institute of Health (NIH) and USFDA also recommended a few drugs to be repurposed i.e., hydroxychloroquine, remdesivir, and favipiravir. However, World Health Organization later recommended against the use of chloroquine, hydroxychloroquine, remdesivir, and lopinavir/ritonavir in the treatment of COVID-19 infections. Combining basic knowledge of viral pathogenesis and pharmacodynamics of drug molecules as well as in silico approaches, many drug candidates have been investigated in clinical trials, some of which have been proven to be partially effective against COVID-19, and many of the other drugs are currently under extensive screening. The repurposing of prospective drug candidates from different stages of evaluation can be a handy wellspring in COVID-19 management and treatment along with approved anti-COVID-19 vaccines. This review article combined the information from completed clinical trials, case series, cohort studies, meta-analyses, and retrospective studies to focus on the current status of repurposing drugs in 2021.

Impact of online education on fear of academic delay and psychological distress among university students following one year of COVID-19 outbreak in Bangladesh.

OBJECTIVES: Extreme fear of academic delay (FAD) and psychological distress among students have arisen as great public health concerns worldwide due to the devastating actions of coronavirus disease 2019 (COVID-19). The precise aim of this study was to assess the impact of ongoing online education on current university students' FAD and psychological stress symptoms following one year of calamitous COVID-19 outbreak in Bangladesh. METHODS: A cross-sectional web-based survey was conducted from March 15 to 30, 2021, for data collection through a snowball simple sampling technique among Bangladeshi University students, where a total of 1,299 respondents (age: ≥ 18 years) responded in the questionnaire. After obtaining informed consent from the participants, we evaluated the association of various sociodemographic factors and the effects of current e-Learning activities on FAD and subsequent psychological distress among university students in Bangladesh. After excluding the partial responses (n = 177), we analyzed the clean data sheet (n = 1,122) by three consecutive statistical methods: univariate, bivariate, and multivariate analyses. RESULTS: Alarmingly, near 60% of the current students exerted extreme FAD and were suffering from severe stress. Besides, 78.1% of students having severe FAD were severely psychologically stressed. Logistic regression analyses revealed that the students of the female gender, rural area, lower-income families, and who suffered from the highest FAD were more significantly (p < 0.05) stressed than their reference groups. CONCLUSION: The current analysis demonstrates that most Bangladeshi university students are battling with the unrivaled trend of FAD and facing severe psychological stress symptoms, which must be alleviated by the concerted efforts of the Government, Universities, and educationalists.

Synthesis, in vitro bioassays, and computational study of heteroaryl nitazoxanide analogs.

Antiprotozoal drug nitazoxanide (NTZ) has shown diverse pharmacological properties and has appeared in several clinical trials. Herein we present the synthesis, characterization, in vitro biological investigation, and in silico study of four hetero aryl amide analogs of NTZ. Among the synthesized molecules, compound 2 and compound 4 exhibited promising antibacterial activity against Escherichia coli (E. coli), superior to that displayed by the parent drug nitazoxanide as revealed from the in vitro antibacterial assay. Compound 2 displayed zone of inhibition of 20 mm, twice as large as the parent drug NTZ (10 mm) in their least concentration (12.5 µg/ml). Compound 1 also showed antibacterial effect similar to that of nitazoxanide. The analogs were also tested for in vitro cytotoxic activity by employing cell counting kit-8 (CCK-8) assay technique in HeLa cell line, and compound 2 was identified as a potential anticancer agent having IC50 value of 172 µg which proves it to be more potent than nitazoxanide (IC50  = 428 µg). Furthermore, the compounds were subjected to molecular docking study against various bacterial and cancer signaling proteins. The in vitro test results corroborated with the in silico docking study as compound 2 and compound 4 had comparatively stronger binding affinity against the proteins and showed a higher docking score than nitazoxanide toward human mitogen-activated protein kinase (MAPK9) and fatty acid biosynthesis enzyme (FabH) of E. coli. Moreover, the docking study demonstrated dihydrofolate reductase (DHFR) and thymidylate synthase (TS) as probable new targets for nitazoxanide and its synthetic analogs. Overall, the study suggests that nitazoxanide and its analogs can be a potential lead compound in the drug development.

Repurposing therapeutic agents against SARS-CoV-2 infection: most promising and neoteric progress.

INTRODUCTION: The pathogenic and highly transmissible etiological agent, SARS-CoV-2, has caused a serious threat COVID-19 pandemic. WHO has declared the epidemic a public health emergency of international concern owing to its high contagiosity, mortality rate, and morbidity. Till now, there is no approved vaccine or drug to combat the COVID-19 and avert this global crisis. AREAS COVERED: In this narrative review, we summarized the updated results (January to August 2020) of the most promising repurposing therapeutic candidates to treat the SARS-CoV-2 viral infection. The repurposed drugs classified under four headlines like antivirals, anti-parasitic, immune-modulating, and miscellaneous drugs were discussed with their in vitro efficacy to recent clinical advancements against COVID-19. EXPERT OPINION: Currently, palliative care, ranging from outpatient management to intensive care, including oxygen administration, ventilator support, intravenous fluids therapy, with some repurposed drugs, are the primary weapons to fight against COVID-19. Until a safe and effective vaccine is developed, an evidence-based drug repurposing strategy might be the wisest option to save people from this catastrophe. Several existing drugs are now under clinical trials, and some of them are approved in different places of the world for emergency use or as adjuvant therapy in COVID-19 with standard of care.

Antimicrobial Diterpenes: Recent Development From Natural Sources.

Antimicrobial resistance has been posing an alarming threat to the treatment of infectious diseases over the years. Ineffectiveness of the currently available synthetic and semisynthetic antibiotics has led the researchers to discover new molecules with potent antimicrobial activities. To overcome the emerging antimicrobial resistance, new antimicrobial compounds from natural sources might be appropriate. Secondary metabolites from natural sources could be prospective candidates in the development of new antimicrobial agents with high efficacy and less side effects. Among the natural secondary metabolites, diterpenoids are of crucial importance because of their broad spectrum of antimicrobial activity, which has put it in the center of research interest in recent years. The present work is aimed at reviewing recent literature regarding different classes of natural diterpenes and diterpenoids with significant antibacterial, antifungal, antiviral, and antiprotozoal activities along with their reported structure-activity relationships. This review has been carried out with a focus on relevant literature published in the last 5 years following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 229 diterpenoids from various sources like plants, marine species, and fungi are summarized in this systematic review, including their chemical structures, classification, and significant antimicrobial activities together with their reported mechanism of action and structure-activity relationships. The outcomes herein would provide researchers with new insights to find new credible leads and to work on their synthetic and semisynthetic derivatives to develop new antimicrobial agents.

Effective syntheses of 2',4'-BNANC monomers bearing adenine, guanine, thymine, and 5-methylcytosine, and the properties of oligonucleotides fully modified with 2',4'-BNANC.

We efficiently synthesized 2'-O,4'-C-aminomethylene-bridged nucleic acid (2',4'-BNANC) monomers bearing the four nucleobases, guanine, adenine, thymine, and 5-methylcytosine and incorporated these monomers into oligonucleotides. Initially, we carried out the transglycosylation reaction on several 2'-O-substituted 5-methyluridines to evaluate the effects of 2'-substitutions on this reaction. Under the optimized conditions, purine nucleobases were successfully introduced, and 2',4'-BNANC monomers bearing adenine or guanine were obtained over several steps. In addition, the improved synthesis of the 2',4'-BNANC monomers bearing thymine or 5-methylcytosine was also achieved. The obtained 2',4'-BNANC monomers were subsequently incorporated into oligonucleotides and the duplex-forming abilities of the modified oligonucleotides were investigated. Duplexes containing 2',4'-BNANC monomers in both or either strands were found to possess excellent thermal stabilities.

Transition Metal Complexes of Naproxen: Synthesis, Characterization, Forced Degradation Studies, and Analytical Method Verification.

The aim of our current research was to synthesize some transition metal complexes of Naproxen, determine their physical properties, and examine their relative stability under various conditions. Characterizations of these complexes were done by 1H-NMR, Differential Scanning Calorimetry (DSC), FT-IR, HPLC, and scanning electron microscope (SEM). Complexes were subjected to acidic, basic, and aqueous hydrolysis as well as oxidation, reduction, and thermal degradation. Also the reversed phase high-performance liquid chromatography (RP-HPLC) method of Naproxen outlined in USP was verified for the Naproxen-metal complexes, with respect to accuracy, precision, solution stability, robustness, and system suitability. The melting points of the complexes were higher than that of the parent drug molecule suggesting their thermal stability. In forced degradation study, complexes were found more stable than the Naproxen itself in all conditions: acidic, basic, oxidation, and reduction media. All the HPLC verification parameters were found within the acceptable value. Therefore, it can be concluded from the study that the metal complexes of Naproxen can be more stable drug entity and offer better efficacy and longer shelf life than the parent Naproxen.

Analgesic and Antipyretic Activities of Methanol Extract and Its Fraction from the Root of Schoenoplectus grossus.

The study aims to evaluate analgesic and antipyretic activities of the methanol extract and its different fractions from root of Schoenoplectus grossus using acetic acid induced writhing and radiant heat tail flick method of pain models in mice and yeast induced pyrexia in rats at the doses of 400 and 200 mg/kg. In acetic acid writhing test, the methanol extract, petroleum ether, and carbon tetrachloride fractions produced significant (P < 0.001 and P < 0.05) inhibition of writhing responses in dose dependent manner. The methanol extract at 400 and 200 mg/kg being more protective with 54% and 45.45% of inhibition compared to diclofenac sodium of 56% followed by petroleum ether fractions of 49.69% and 39.39% at the same doses. The extracts did not produce any significant antinociceptive activity in tail flick test except standard morphine. When studied on yeast induced pyrexia, methanol and petroleum ether fractions significantly lowered the rectal temperature time dependently in a manner similar to standard drug paracetamol and distinctly more significant (P < 0.001) after second hour. These findings suggest that the root extracts of S. grossus possess significant peripherally acting analgesic potential and antipyretic property. The phytochemical screening showed the presence of flavonoids, alkaloids, and tannins.

In vitro antioxidant and cholinesterase inhibitory activities of methanolic fruit extract of Phyllanthus acidus.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder clinically characterized by loss of memory and cognition. Cholinergic deficit and oxidative stress have been implicated in the pathogenesis of AD. Therefore, inhibition of acetylcholinesterase and oxidation are the two promising strategies in the development of drug for AD. Phyllanthus acidus, belonging to the family Euphorbiaceae, is a tree and has been used in traditional medicine to treat several pain, inflammatory and oxidative stress related disorders such as rheumatism, bronchitis, asthma, respiratory disorder, also important to promote intellect and enhance memory, thus supporting its possible anti-Alzheimer's properties. In this study, P. acidus was evaluated for its cholinesterase inhibitory and antioxidant activities. METHODS: In this study, we evaluated the antioxidant potential and neuroprotective activity of P. acidus by assessing total phenol content (FCR assay), total flavonoid content, total antioxidant capacity, Fe (3+) reducing power capacity, DPPH (2, 2-diphenyl-1-picrylhydrazyl) and hydroxyl radical scavenging capacity, lipid peroxidation inhibition activity & metal chelating activity. In addition acetylcholinestrase (AChE) and butyrylcholinestrase (BChE) inhibitory activities were performed using Ellman's method. RESULTS: Total phenolic content and total flavonoid content of the extract were 116.98 mg of gallic acid equivalent and 168.24 mg of quercetin equivalent per gm of dried extract. The methanolic extract of P. acidus (MEPA) showed considerable total antioxidant activity and reducing capacity. In DPPH scavenging assay and hydroxyl radical scavenging assay, the MEPA showed 84.33 % and 77.21 % scavenging having IC50 of 15.62 and 59.74 µg/ml respectively. In lipid peroxidation inhibition activity MEPA showed moderate inhibition of peroxidation at all concentrations with IC50 value of 471.63 µg/ml and exhibited metal chelating activity with IC50 value 308.67 µg/ml. The MEPA exhibited inhibition of rat brain acetylcholinesterase and human blood butyrylcholinesterase in a dose dependent manner and the IC50 value was found to be 1009.87 µg/ml and 449.51 µg/ml respectively. CONCLUSION: These results of the present study reveal that MEPA has considerable amount of antioxidant activity as well as anti-acetylcholinesterase and anti-butyrylcholinesterase activity which suggest its effectiveness against Alzheimer's disease and other neurodegenerative disorders.

Crispene E, a cis-clerodane diterpene inhibits STAT3 dimerization in breast cancer cells.

Crispene E, a new clerodane-type diterpene, inhibited STAT3 dimerization in a cell-free fluorescent polarisation assay and was found to have significant toxicity against STAT3-dependent MDA-MB 231 breast cancer cell line and selectively inhibited the expression of STAT3 and STAT3 target genes cyclin D1, Fascin and bcl-2. Molecular docking studies suggest the molecule inhibits STAT3 by interacting with its SH2 domain. The compound has been isolated from Tinospora crispa and characterized using standard spectroscopic techniques.