Assessing effectiveness of adding niosomal atorvastatin 1% ointment to topical calcineurin inhibitor treatment in non-segmental vitiligo.

BACKGROUND: Treatment of vitiligo is still a big challenge for dermatologists. The efficacy of statins in the treatment of vitiligo is controversial. AIM AND OBJECTIVE: We studied possible therapeutic effect of topical 1% niosomal atorvastatin ointment combined with topical 0.1% tacrolimus in treatment of non-segmental vitiligo. METHODS: This is a triple blind, pilot, randomized placebo-controlled trial (RCT) that was performed in dermatology clinic. All the patients used topical 0.1% tacrolimus cream twice daily (BD). Moreover, the intervention group participants used topical 1% niosomal atorvastatin ointment, and control group participants were prescribed placebo ointment, BD. Patients were evaluated using vitiligo area surface index (VASI) score and patients' satisfaction at baseline and after 3 months treatment. RESULTS: The mean patient satisfaction in the intervention and control groups were 5 ± 1.4 and 3.5 ± 1.9; the difference between groups was not statistically significant (p = 0.9). We found statistically significant difference in VASI score before and after treatment in both intervention and control groups (p = 0.01 and p = 0.03, respectively). However, comparison of the VASI score between groups was not statistically significant (p = 0.62). We also found no significant correlation between VASI score and other variables. CONCLUSION: The result of this study indicates that adding of niosomal atorvastatin 1% ointment to topical calcineurin inhibitor has no additional effect on non-segmental type of vitiligo. Further large studies with different combinations are recommended before any conclusive result can be concluded on efficacy of statins in vitiligo.

Niosomal Doxycycline and Triamcinolone: A Novel Approach to Minimize Cytotoxicity in Endodontic Medicaments.

Introduction: Mechanical root canal preparations and irrigation solutions are essential for reducing microbial counts in the root canal system. However, these methods do not completely eliminate microorganisms. Intracanal medicaments are used to further decrease microbial counts. This study aims to assess the cytotoxicity of various intracanal medicaments. Materials and methods: In this in vitro study, murine fibroblast cell lines (L929) were cultured in a controlled environment. The MTT assay was employed to evaluate the cytotoxicity of different medicament combinations, including calcium hydroxide and triamcinolone (D1), niosomal doxycycline and triamcinolone (D2), calcium hydroxide (D3), and a combination of doxycycline and triamcinolone (D4). Statistical analysis was performed using ANOVA and Dunnett's test. Results: The results indicated that D1 and D2 had lower cytotoxicity, while D4 exhibited the highest cytotoxicity. D1 was found to be non-cytotoxic up to a concentration of 500 µg/mL over a period of 72 hours. D2 and D3 showed similar effects up to concentrations of 250 µg/mL and 100 µg/mL, respectively, for 72 hours. In contrast, D4 exhibited cytotoxicity at concentrations above 75 µg/mL at 72 hours. Conclusion: This study suggests that encapsulating doxycycline in niosomal structures (D2) reduces cytotoxicity in murine fibroblast cell lines (L929) for at least 24 and 48 hours. These findings offer promising implications for the development of endodontic medicaments with improved biocompatibility.

Comparative Efficacy of Analgesics for Pain Relief in Patients with Symptomatic Irreversible Pulpitis Prior to Emergency Endodontic Treatment: A Randomized Controlled Trial.

Introduction: This study aimed to compare the efficacy of ibuprofen, Novafen, mefenamic acid (MA), and celecoxib for pain relief in patients with symptomatic irreversible pulpitis prior to emergency endodontic treatment. Materials and Methods: This clinical trial was conducted on 120 patients with moderate to severe pain due to symptomatic irreversible pulpitis seeking emergency endodontic treatment. The patients were randomly divided into 4 groups to receive Novafen, MA, Celecoxib, and ibuprofen. The pain score of patients was measured before and 1 hour after analgesic intake using a visual analog scale (VAS). The success of analgesic treatment was analyzed by the binary logistic regression model. Results: A total of 117 patients including 76 females and 41 males with a mean age of 30.29 years completed the study and were statistically analyzed. Ibuprofen had the highest analgesic efficacy followed by Novafen, and caused a significantly greater reduction in pain score compared with MA and celecoxib [OR (Ibuprofen vs MA)=1.28, OR (Ibuprofen vs Celecoxib)=3.74, OR (Novafen vs MA)=2.94, OR (Novafen vs Celecoxib)=2.94, P<0.05]. Ibuprofen and Novafen had no significant difference in analgesic efficacy (P>0.05). Baseline pain score was a predictive factor for the success of analgesics (P<0.05). The success of analgesic treatment decreased by 0.68 times with each unit increase in pain score (P<0.05). Gender and age of patients had no significant effect on success of analgesics (P>0.05). Conclusion: Both ibuprofen and Novafen can serve as the analgesics of choice for pain relief in patients with symptomatic irreversible pulpitis with moderate to severe pain when emergency endodontic treatment cannot be immediately performed.

Assessment of the Effect of Sub-Cutaneous Adalimumab on Prognosis of COVID-19 Patients: a Non-Randomized Pilot Clinical Trial Study in Iran.

BACKGROUND: Adalimumab is an anti-inflammatory medicine used to treat a variety of disorders, although its effectiveness in improving the clinical status of COVID-19 patients is debatable. The goal was to evaluate the efficacy of adalimumab as an alternate treatment in COVID-19 patients. METHODS: This non-randomized pilot clinical trial study included 18 patients with severe COVID-19 status hospitalized at the Afzalipour Hospital in Kerman from February 2022 to March 2022. Patients were divided into two groups: nine patients in the control group received dexamethasone, remdesivir, and heparin in addition to supportive therapies. The case group also included nine patients who received adalimumab injection (CinnoRA®, CinnaGen, Iran) in addition to the treatment administered to the control group. RESULTS: Although the effect of adalimumab injection on clinical factors, including mechanical ventilation required, the number of days oxygen needed, the length of stay in the intensive care unit (ICU), and saturation of peripheral oxygen (SpO2) level and respiratory rate (RR), were not significantly different between groups, the intra-group SpO2 level before and after receiving oxygen was significantly different in the case group (p ≤ 0.001 and p = 0.002). In addition, laboratory tests for lactate dehydrogenase (LDH) and C-reactive protein (CRP) revealed no statistically significant differences between the two groups. Nonetheless, a positive intra-group effect of the medication was detected on these two parameters. No short-term side effects of drug injection were observed. CONCLUSIONS: This study demonstrated the efficacy of adalimumab as an alternate medication for improving SpO2, LDH, and CRP levels in COVID-19 patients.

Effect of l -Dopa in acute temozolomide-induced cognitive impairment in male mice: a possible antineuroinflammatory role.

Temozolomide is used commonly in the treatment of some types of cancers, but it may also result in cognitive impairments such as memory deficits. l -Dopa, a well known medicine for the central nervous system, has been shown to have positive effects on some cognitive disorders. Here we sought to investigate the effect of l -Dopa on temozolomide-induced cognitive impairments. BALB/c mice were subjected to 3-days temozolomide and 6-days concomitant l -Dopa/benserazide administration in six groups (control, l -Dopa 25 mg/kg, l -Dopa 75 mg/kg, temozolomide, temozolomide +  l -Dopa 25 mg/kg, and temozolomide +  l -Dopa 75 mg/kg). Open field test, object location recognition, novel object recognition test, and shuttle-box test were carried out to determine the locomotor, anxiety-like behavior, and memory function of subjects. TNF-α and brain-derived neurotrophic factor (BDNF) gene expression in the hippocampus was measured by real-time PCR. Mice treated with temozolomide showed recognition memory impairment, along with hippocampal TNF-α and BDNF mRNA expression level raise, and detection of histological insults in hematoxylin and eosin hippocampal slides. Mice that received temozolomide +  l -Dopa showed normal behavioral function and lower TNF-α and BDNF hippocampal mRNA expression levels, and histologically normal hippocampal CA1 region in comparison with mice in the temozolomide group. Our results provide evidence that l -Dopa prevents temozolomide-induced recognition memory deficit in mice at the acute phase probably via l -Dopa antineuroinflammatory effects.

Synthesis and physicochemical characterization of Zn-Al layered double hydroxides (LDHs) as a delivery system for amphotericin B: In vitro and in silico antileishmanial study.

Leishmaniasis as a widespread neglected vector-borne protozoan disease is a major public health concern in endemic areas due to 12 million people affected worldwide and 60,000 deaths annually. Several problems and side effects in using current chemotherapies leads to progression of new drug delivery systems against leishmaniasis. For instance, layered double hydroxides (LDHs) so-called anionic clays due to their proper characteristics, have been considered recently. In the present study, LDH nanocarriers were prepared using co-precipitation method. Then, the intercalation reactions with amphotericin B were conducted via indirect ion exchange assay. Finally, after characterization of prepared LDHs, the anti-leishmanial effects of Amp-Zn/Al-LDH nanocomposites against Leishmania major were evaluated using an in vitro and in silico model. According to results, current study demonstrated that Zn/Al-NO3 LDH nanocarriers can be used as a new promising delivery system by intercalating amphotericin B into its interlayer space for leishmaniasis treatment by eliminating the L. major parasites by remarkable immunomodulatory, antioxidant and apoptotic effects.

The prevalence and predictors of herb-drug interactions among Iranian cancer patients during chemotherapy courses.

BACKGROUND: The concurrent usage of herbal medicines with conventional therapies is an important concern in cancer treatment which can lead to unexpected consequences like herb-drug interactions. This study aimed to determine the prevalence of potential herb-drug interactions and to predict factors associated with herb-drug interactions for cancer patients. METHODS: This cross-sectional study was conducted among a convenience sample of 315 cancer patients referring to the oncology clinics of Kerman city in 2018. Data were collected via comprehensive face-to-face interviews and medical chart reviews. A drug interaction checker was used to determine herb-drug interactions. The information of patients was compared based on herb-drug interactions using bivariable logistic regression models, and predictors were determined by the multivariable logistic regression model. All analyses were performed by Stata software version 16. RESULTS: Of 262 patients (83.2% of the patients) who used herbal medicines, 209 patients [79.8% (95% Confidence Intervals (CI): 75.2 - 85.1)] had potential herb-drug interactions. Chamomile was the most popular herbal medicine (n = 163, 78.0%), and minor and moderate herb-drug interactions were caused by green tea (n = 34, 16.3%) and peppermint (n = 78, 37.5%). The number of chemotherapeutic agents (OR: 1.92, 95% CI: 1.43-2.58; P-value < 0.0001) and the experienced of pain during chemotherapy courses (OR = 2.22, 95%CI:1.00-4.94; P-value = 0.04) were some of the predictors of herb-drug interactions among cancer patients. CONCLUSION: Herbal medicine use during chemotherapy was found prevalent among cancer patients; of them, the experience of potential herb-drug interactions was highly frequent. Oncologists and clinical pharmacologists are recommended to take into account challenges associated with herb-drug interactions in their routine practices, particularly during chemotherapy among these patients.

Empagliflozin induces apoptotic-signaling pathway in embryonic vasculature: In vivo and in silico approaches via chick's yolk sac membrane model.

The present investigation was conducted to evaluate the vascular-toxicity of empagliflozin (EMP) in embryonic vasculature. Firstly, the vascular-toxicity of the drug as well as its interaction with apoptotic regulator proteins was predicted via in silico approach. In the next step, the apoptotic-signaling pathway in embryonic vasculature was evaluated using a chick's YSM model. In silico simulation confirmed vascular-toxicity of EMP. There was also an accurate affinity between EMP, Bax and Bcl-2 (-7.9 kcal/mol). Molecular dynamics assay revealed complex stability in the human body conditions. Furthermore, EMP is suggested to alter Bcl-2 more than BAX. Morphometric quantification of the vessels showed that the apoptotic activity of EMP in embryonic vasculature was related to a marked reduction in vessel area, vessel diameter and mean capillary area. Based on the qPCR and immunohistochemistry assays, enhanced expression level of BAX and reduced expression level of Bcl-2 confirmed apoptotic responses in the vessels of the YSM. We observed that induction of an apoptotic signal can cause the embryonic defect of the vascular system following EMP treatment. The acquired data also raised suspicions that alteration in apoptotic genes and proteins in the vasculature are two critical pathways in vascular-toxicity of EMP.

The development of disposable electrochemical sensor based on MoSe2-rGO nanocomposite modified screen printed carbon electrode for amitriptyline determination in the presence of carbamazepine, application in biological and water samples.

The present attempt developed a simple sensing system based on the modification of screen-printed carbon electrode (SPCE) with MoSe2/reduced graphene oxide (rGO) nanocomposite (MoSe2-rGO/SPCE) to voltammetrically co-detect amitriptyline and carbamazepine. Different techniques such as field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray (EDX), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR) were employed to characterize MoSe2-rGO nanocomposite morphology and structure. Moreover, chronoamperometry, differential pulse voltammetry (DPV) and linear sweep voltammetry (LSV) were utilized to explore the electrochemical oxidation of amitriptyline. Data revealed a great current sensitivity for the MoSe2-rGO/SPCE towards amitriptyline. The peak currents of amitriptyline oxidation on the MoSe2-rGO/SPCE had linear dynamic range (0.02-380.0 µM) and a narrow limit of detection (0.007 µM). The MoSe2-rGO/SPCE was successful in sensing carbamazepine and amitriptyline in real specimens, with appreciable recovery rates.

Successful Application of Alpha Lipoic Acid Niosomal Formulation in Cerebral Ischemic Reperfusion Injury in Rat Model.

Purpose: Free radicals such as hydroxyl and peroxide are contributing factors to neuronal destruction in cerebral ischemia. Alpha-lipoic acid (ALA) is one of the potent known antioxidants. Preparation of ALA niosomes allows IV injection and can increase bioavailability and penetration into the central nervous system (CNS). Methods: Film hydration method was used to prepare different niosomes composed of Span®, Tween®, and cholesterol at different molar ratio. ALA and niosome-forming compounds were dissolved in chloroform, before removing the organic solvent by rotary evaporator. Animals were randomly divided into four groups: Sham, control group, intravenous (IV) injection of empty niosomes plus intraperitoneal (IP) injection of ALA solution, and finally, IV injection of ALA niosomes. Rats were subjected to deep anesthesia before inducing cerebral ischemia, then, their internal common carotid arteries were clamped for 15 min and reperfusion was done for 30 min. Niosomal ALA was injected intravenously just before declamping. Results: Mean volume diameter of the prepared niosomes was between 4.36 ± 0.82 and 19.95 ± 1.21 µm in different formulations. Encapsulation efficiency percent (EE%) of ALA in the selected formulation, Span60/Tween60/cholesterol (35:35:30 molar ratio), was 94.5 ± 0.2, and 59.27 ± 5.61% of ALA was released after 4h. In the niosomal group, the rate of reduction in complications of cerebral ischemia such as histopathologic changes and acute damage (from score 3 to 1) in CNS was higher than other groups. Conclusion: The obtained results show that niosomes can be used as effective drug delivery systems for ALA in cerebral ischemia.

The Impact of D614G Mutation of SARS-COV-2 on the Efficacy of Anti-viral Drugs: A Comparative Molecular Docking and Molecular Dynamics Study.

D614G is one of the most reported mutations in the spike protein of SARS-COV-2 that has altered some crucial characteristics of coronaviruses, such as rate of infection and binding affinities. The binding affinity of different antiviral drugs was evaluated using rigid molecular docking. The reliability of the docking results was evaluated with the induced-fit docking method, and a better understanding of the drug-protein interactions was performed using molecular dynamics simulation. The results show that the D614G variant could change the binding affinity of antiviral drugs and spike protein remarkably. Although Cytarabine showed an appropriate interaction with the wild spike protein, Ribavirin and PMEG diphosphate exhibited a significant binding affinity to the mutated spike protein. The parameters of the ADME/T analysis showed that these drugs are suitable for further in-vitro and in-vivo investigation. D614G alteration affected the binding affinity of the RBD and its receptor on the cell surface.

Characteristics and in vitro anti skin aging activity and UV radiation protection of morin loaded in niosomes.

BACKGROUND: One of the dermatologic problems in elderly people is skin aging, which is a natural and complex biological process. Morin is a flavonoid with high radical scavenging activity as well as antityrosinase effects but its low water solubility has restricted its application. AIMS: This research aimed to develop, characterize, and optimize morin niosomes composed of non-ionic surfactants, and evaluate the in vitro UV protection and antiaging effectiveness. METHODS: Niosomes were prepared by the film hydration method with sorbitan monostearate (Span® 40), polyoxyethylenesorbitan monopalmitate (Tween® 40), and cholesterol. The niosomes were characterized in terms of size, zeta potential, morphology, in vitro release behavior, and drug entrapment efficiency (EE). Afterward, antiaging activity, including antityrosinase, antioxidant, intracellular reactive oxygen species (ROS) scavenging, and sun protection factor (SPF) were evaluated. RESULTS: The optimized niosomes appeared as unilamellar vesicles with a spherical shape, with size, zeta potential, and EE values of 6.13 ± 0.40 µm, -0.81 ± 0.32 mV, and 89.35% ± 2.80%, respectively. The noisome formulation remained stable at -4°C for 3 months. The release profiles of morin loaded in niosomes revealed the extended release over 8 h and followed zero-order release kinetics. Morin-loaded niosomes exhibited no significant toxicity toward the L929 cell line. The niosome loaded with morin showed anti skin aging activity, including antityrosinase effects (IC50 = 13.17 ± 1.58 µg/ml), antioxidant (IC50 = 28.49 ± 2.05 µg/ml), and ROS scavenging activity. For 1% and 5% (w/w) morin niosomes in eucerin base cream, the SPF was 39.03 ± 1.01 and 38.15 ± 0.82, respectively, whereas the noisome-free morin cream exhibited an SPF of 4.47 ± 0.56. CONCLUSION: Morin-loaded niosome has been shown to provide sun protection and antiaging effects, suggesting that it could be used in pharmaceutical and cosmetic products.

In silico SELEX screening and statistical analysis of newly designed 5mer peptide-aptamers as Bcl-xl inhibitors using the Taguchi method.

Drug development for cancer treatment is a complex process that requires special efforts. Targeting crucial proteins is the most essential purpose of drug design in cancers. Bcl-xl is an anti-apoptotic protein that binds to pro-apoptotic proteins and interrupts their signals. Pro-apoptotic Bcl-xl effectors are short BH3 sequences that form an alpha helix and bind to anti-apoptotic proteins to inhibit their activity. Computational systematic evolution of ligands by exponential enrichment (SELEX) is an exclusive approach for developing peptide aptamers as potential effectors. Here, the amino acids with a high tendency for constructing an alpha-helical structure were selected. Due to the enormous number of pentapeptides, Taguchi method was used to study a selected number of peptides. The binding affinity of the peptides to Bcl-xl was assessed using molecular docking, and after analysis of the obtained results, a final set of optimized peptides was arranged and constructed. For a better comparison, three chemical compounds with approved anti-Bcl-xl activity were selected for comparison with the top-ranked 5mer peptides. The optimized peptides showed considerable binding affinity to Bcl-xl. The molecular dynamics (MD) simulation indicated that the designed peptide (PO5) could create considerable interactions with the BH3 domain of Bcl-xl. The MM/GBSA calculations revealed that these interactions were even stronger than those created by chemical compounds. In silico SELEX is a novel approach to design and evaluate peptide-aptamers. The experimental design improves the SELEX process considerably. Finally, PO5 could be considered a potential inhibitor of Bcl-xl and a potential candidate for cancer treatment.

Dexamethasone: Insights into Pharmacological Aspects, Therapeutic Mechanisms, and Delivery Systems.

Dexamethasone (DEX) has been widely used to treat a variety of diseases, including autoimmune diseases, allergies, ocular disorders, cancer, and, more recently, COVID-19. However, DEX usage is often restricted in the clinic due to its poor water solubility. When administered through a systemic route, it can elicit severe side effects, such as hypertension, peptic ulcers, hyperglycemia, and hydro-electrolytic disorders. There is currently much interest in developing efficient DEX-loaded nanoformulations that ameliorate adverse disease effects inhibiting advancements in scientific research. Various nanoparticles have been developed to selectively deliver drugs without destroying healthy cells or organs in recent years. In the present review, we have summarized some of the most attractive applications of DEX-loaded delivery systems, including liposomes, polymers, hydrogels, nanofibers, silica, calcium phosphate, and hydroxyapatite. This review provides our readers with a broad spectrum of nanomedicine approaches to deliver DEX safely.

Recent advances in Bio-conjugated nanocarriers for crossing the Blood-Brain Barrier in (pre-)clinical studies with an emphasis on vesicles.

The brain is one of the most challenging organs for drug delivery. It is preserved by the blood-brain barrier (BBB), which controls the transport of components into and out of the brain. Although various approaches have been utilized to cross the BBB, the drug delivery into the brain is still less successful than the other human body parts. Comprehensive knowledge about the mechanisms and functionalities of brain delivery for different components is required to overcome this complex barrier. In this review, we have discussed the BBB structure, its characteristics, and the BBB's mechanisms for transporting components between the brain and blood. Furthermore, the barriers in front of drug delivery systems, the strategies which should be employed for overcoming these barriers, and different pathways for brain targeting are discussed. Then, the drug delivery systems utilized for crossing the BBB, especially nanocarriers and novel approaches, are considered. Finally, the bioconjugated vesicles as versatile nanocarriers that combine the bioconjugation approach and vesicles are reviewed. This review focuses on the biomolecules used in nano vesicular systems for overcoming the BBB. Various biomolecules such as amino acids, peptides, proteins, antibodies, and carbohydrates could be used for bioconjugation. Bioconjugated vesicles like liposomes and niosomes utilize the related receptor or transporter to cross the BBB. These drug delivery systems have shown enhanced drug loading into the brain, which is discussed.

The Prevalence of Polypharmacy and Potential Drug-Drug Interactions among Iranian Cancer Patients: Which Patients were at Risk?

INTRODUCTION: Drug-Drug interactions (DDIs) are one of the considerable consequences of polypharmacy. Due to the influence of polypharmacy and drug interactions on cancer treatment and patients` health outcomes, this study aimed to determine the prevalence of polypharmacy and potential DDIs among adult cancer patients in Kerman province, southeast of Iran. METHODS: In this cross-sectional study, 315 cancer patients who referred to Kerman city oncology clinics were assessed in 2018. Data were collected through face-to-face interviews and medical charts were reviewed. Polypharmacy was defined as the use of at least five drugs simultaneously. Potential DDIs were checked using the "Drugs.com" online database. A bivariable and a multivariable logistic regression were used to determine the associated factors of outcome variables, polypharmacy status, and potential DDI in SPSS software version 23. RESULTS: Of 315 cancer patients, 191 patients (60.6%; 95% CI: 54.9, 66) used at least five drugs during chemotherapy courses. The prevalence of potential DDIs was 59.6% (n = 140, 95% confidence interval [CI]: 53.6-66.0. Experience co-morbid diseases (OR: 6.60; 95% CI: 3.82, 11.42; p value ≤ .0001), and positive metastatic status (OR: 2.80; 95% CI: 1.62, 4.82; p value ≤ .0001) could predict the polypharmacy during chemotherapy courses. Patients who suffered gastrointestinal cancers (OR: 5.55; 95% CI: 2.26, 13.62; p value ≤ .0001) and the number of prescribed or Over The Counter (OTC) drugs (OR: 1.29; 95% CI: 1.12, 1.48; p value < .0001) predicted the occurrence of potential DDIs among cancer patients. CONCLUSIONS: Regarding the high prevalence of polypharmacy and potential drug interactions among Iranian cancer patients during chemotherapy courses, it is advisable for physicians, nurses, and pharmacists to be vigilant to improve prescribing patterns. In addition, with intensive monitoring, alternative treatment strategies can be replaced.

Chitosan: A versatile bio-platform for breast cancer theranostics.

Breast cancer is considered one of the utmost neoplastic diseases globally, with a high death rate of patients. Over the last decades, many approaches have been studied to early diagnose and treat it, such as chemotherapy, hormone therapy, immunotherapy, and MRI and biomarker tests; do not show the optimal efficacy. These existing approaches are accompanied by severe side effects, thus recognizing these challenges, a great effort has been done to find out the new remedies for breast cancer. Main finding: Nanotechnology opened a new horizon to the treatment of breast cancer. Many nanoparticulate platforms for the diagnosis of involved biomarkers and delivering antineoplastic drugs are under either clinical trials or just approved by the Food and Drug Administration (FDA). It is well known that natural phytochemicals are successfully useful to treat breast cancer because these natural compounds are safer, available, cheaper, and have less toxic effects. Chitosan is a biocompatible and biodegradable polymer. Further, it has outstanding features, like chemical functional groups that can easily modify our interest with an exceptional choice of promising applications. Abundant studies were directed to assess the chitosan derivative-based nanoformulation's abilities in delivering varieties of drugs. However, the role of chitosan in diagnostics and theranostics not be obligated. The present servey will discuss the application of chitosan as an anticancer drug carrier such as tamoxifen, doxorubicin, paclitaxel, docetaxel, etc. and also, its role as a theranostics (i.e. photo-responsive and thermo-responsive) moieties. The therapeutic and theranostic potential of chitosan in cancer is promising and it seems that to have a good potential to get to the clinic.

3D-QSAR, molecular docking, molecular dynamics, and ADME/T analysis of marketed and newly designed flavonoids as inhibitors of Bcl-2 family proteins for targeting U-87 glioblastoma.

Glioblastoma is the most common and destructive brain tumor with increasing complexity. Flavonoids are versatile natural compounds with the approved anticancer activity, which could be considered as a potential treatment for glioblastoma. A quantitative structure-activity relationship (QSAR) can provide adequate data for understanding the role of flavonoids structure against glioblastoma. The IC50 of various flavonoids for the U-87 cell line was used to prepare an adequate three-dimensional QSAR (3D-QSAR) model. The validation of the model was carried out using some statistical parameters such as R2 and Q2 . Based on the QSAR model, the activities of other marketed and newly designed flavonoids were predicted. Molecular docking study and molecular dynamics (MD) simulation were conducted for better recognition of the interactions between the most active compounds and Bcl-2 family proteins. Moreover, an AMDE/T analysis was performed for the most active flavonoids. A reliable 3D-QSAR was performed with R2 and Q2 of 0.91 and 0.82. The molecular docking study revealed that BCL-XL has a higher binding affinity with the most active compounds, and the MD simulation showed that some residues of the BH3 domain, such as Phe97, Tyr101, Arg102, and Phe105 create remarkable hydrophobic interactions with the ligands. ADME/T analysis also showed the potential of the active compounds for further investigation. 3D-QSAR study is a beneficial method to evaluate and design anticancer compounds. Considering the results of the molecular docking study, MD simulation, and ADME/T analysis, the designed compound 54 could be considered as a potential treatment for glioblastoma.

[TBP]2SO4 ionic liquid catalyst for 4MCR of pyridazinoindazole, indazolophthalazine and pyrazolophthalazine derivatives.

Tetrabutyl phosphonium sulfate ([TBP]2SO4), as novel room-temperature ionic liquid (RTIL), was synthesized by a simple cost-effective method, characterized by 1H, 13C, 31P NMR and FT-IR spectrophotometry. The newly prepared catalyst was used as an efficient catalyst in some four multicomponent reactions (4MCRs) e. g., to synthesis pyridazino[1,2-a]indazole, indazolo[2,1-b]phthalazine and pyrazolo[1,2-b]phthalazine. This green method has several advantages such as short reaction time, using simple methods to prepare catalysts and products, easy operation and high efficiency of products. In addition, the catalyst can be easily recovered and reused several times with reduced average activity.