In Silico Analysis of Bioactive Compounds from Leaves of Abrus precatorius L. (Rosary Pea) Against Breast Cancer.

Introduction Breast cancer is one of the most common causes of cancer among women. Since the administration of chemotherapy drugs can cause several adverse effects, thus it leads to research on effective treatment from natural sources. Leaves of Abrus precatorius L., a member of the Fabaceae family,contain several medicinal properties. It has drawn interest as an anti-cancer agent since its leaves contain different phytochemicals that can cause apoptosis in a variety of cancer types. Methods A total of 97 compounds were identified from the ethyl acetate extract of A. precatorius leaves by gas chromatography/mass spectrometry (GC/MS) analysis. Of those, eight compounds were selected based on the percentage area above 2. Cheminformatics software such as Molinspiration (Molinspiration Cheminformatics free web services, Slovensky Grob, Slovakia) was used to predict the molecular properties and bioactivity. PASS software (NCSS LLC, Kaysville, Utah, United States) was used to predict the scores of anticancer properties such as antioxidant, anti-inflammatory, immunosuppressant, antineoplastic, and cytoprotective. Osiris Property Explorer software was used to determine pharmacokinetic profile and toxicity prediction, and molecular docking was performed to determine the binding affinity towards the receptors. Results Out of eight compounds, one was selected based on the scores of the above software, then docking studies were done by using AutoDock Vina 4.2.6 (Center for Computational Structural Biology, La Jolla, California, United States). The results were compared with the reference compound, 5-fluorouracil, and 1,4-dimethyl-4 pentenyl acetate was identified as the most promising active compound found in this study. It shows better binding affinity towards the progesterone receptor (-6.0) when compared to the reference compound. Conclusion Based on the results, it has been proved that 1,4-dimethyl-4 pentenyl acetate may be used as an alternative for the management of breast cancer.

Osiris17 is indispensable for morphogenesis of intestinal tract in Locusta migratoria.

The Osiris gene family is believed to play important roles in insect biology. Previous studies mainly focused on the roles of Osiris in Drorophila, how Osiris operates during the development of other species remains largely unknown. Here, we investigated the role of LmOsi17 in development of the hemimetabolous insect Locusta migratoria. LmOsi17 was highly expressed in the intestinal tract of nymphs. Knockdown of LmOsi17 by RNA interference (RNAi) in nymphs resulted in growth defects. The dsLmOsi17-injected nymphs did not increase in body weight or size and eventually died. Immunohistochemical analysis showed that LmOsi17 was localized to the epithelial cells of the foregut and the gastric caecum. Histological observation and hematoxylin-eosin staining indicate that the foregut and gastric caecum are deformed in dsLmOsi17 treated nymphs, suggesting that LmOsi17 is involved in morphogenesis of foregut and gastric caecum. In addition, we observed a significant reduction in the thickness of the new cuticle in dsLmOsi17-injected nymphs compared to control nymphs. Taken together, these results suggest that LmOsi17 contributes to morphogenesis of intestinal tract that affects growth and development of nymphs in locusts.

Molecular docking analysis of flavonoids with AChE and BACE-1.

Flavonoids are promising therapeutics for the treatment of Alzheimer's disease (AD). Therefore, it is of interest to study the anti-AD potential of 35 flavonoids towards the inhibition of AchE and BACE-1. Hence, the physicochemical, pharmacokinetic parameters, toxicity risk and drug-likeliness of the selected 35 flavonoids were computed. Further, the molecular docking analysis of flavonoids with AChE and BACE-1 were completed. A binding energy of -10.42 kcal/mol Epicatechin gallate, -10.16 kcal/mol sterubin and -10.11 kcal/mol Fisetin was observed with AchE as potential inhibitors. Similarly, Biochainin-A -9.81kcal/mol, Sterubin -8.96 kcal/mol and Epicatechin gallate -7.4 7 kcal/mol showed with BACE-1. Thus, these flavonoids are potential leads for structure-based design of effective anti-Alzheimer's agents.

Osiris17 is essential for stable integrin localization and function during insect wing epithelia remodeling.

The dynamic adhesion between cells and their extracellular matrix is essential for the development and function of organs. During insect wing development, two epithelial sheets contact each other at their basal sites through the interaction of ßPS integrins with the extracellular matrix. We report that Osiris17 contributes to the maintenance of ßPS integrins localization and function in developing wing of Drosophila and locust. In flies with reduced Osiris17 expression the epithelia sheets fail to maintain the integrity of basal cytoplasmic junctional bridges and basal adhesion. In contrast to the continuous basal integrin localization in control wings, this localization is disrupted during late stages of wing development in Osiris17 depleted flies. In addition, the subcellular localization revealed that Osiris17 co-localizes with the endosomal markers Rab5 and Rab11. This observation suggests an involvement of Osiris17 in endosomal recycling of integrins. Indeed, Osiris17 depletion reduced the numbers of Rab5 and Rab11 positive endosomes. Moreover, overexpression of Osiris17 increased co-localization of Rab5 and ßPS integrins and partially rescued the detachment phenotype in flies with reduced ßPS integrins. Taken together, our data suggest that Osiris17 is an endosome related protein that contributes to epithelial remodeling and morphogenesis by assisting basal integrins localization in insects.

Exploring the therapeutic potential of galidesivir analogs against Zaire ebolavirus protein 24 (V24): database screening, molecular docking, drug-relevant property evaluation and molecular dynamics simulations.

The recent outbreak of the Ebola virus (EBOV) has marked it as one of the most severe health threats globally. Among various anti-EBOV inhibitors studied, galidesivir (BCX4430) has shown remarkable efficacy. This study aims to identify novel potential anti-EBOV drugs among galidesivir analogs, focusing on the Zaire ebolavirus (Z-EBOV), which exhibits a mortality rate of 90%. We subjected 200 candidate compounds to molecular docking calculations, followed by an evaluation of the bioactivity of the top 25 compounds using the OSIRIS Property Explorer. Initial 50 ns molecular dynamics (MD) simulations were then performed. According to our findings, only six compounds exhibited positive drug scores. We further performed molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) calculations of binding energy over 50 ns, selecting the two top-performing compounds for extended 150 ns MD simulations. CID 117698807 and CID 117712809 showed higher binding stability compared to galidesivir, with ΔGbinding values of -36.7 and -53.4 kcal/mol, respectively. Both compounds demonstrated high stability within the Z-EBOV-V24 active site over the 150 ns MD simulations. Hence, our study proposes CID 117698807 and CID 117712809 as potential anti-Z-EBOV-V24 drug candidates, warranting further investigation.Communicated by Ramaswamy H. Sarma.

Computer Analysis of the Inhibition of ACE2 by Flavonoids and Identification of Their Potential Antiviral Pharmacophore Site.

In the present study, we investigated the antiviral activities of 17 flavonoids as natural products. These derivatives were evaluated for their in vitro antiviral activities against HIV and SARS-CoV-2. Their antiviral activity was evaluated for the first time based on POM (Petra/Osiris/Molispiration) theory and docking analysis. POM calculation was used to analyze the atomic charge and geometric characteristics. The side effects, drug similarities, and drug scores were also assumed for the stable structure of each compound. These results correlated with the experimental values. The bioinformatics POM analyses of the relative antiviral activities of these derivatives are reported for the first time.

The Adapted POM Analysis of Avenanthramides In Silico.

POM analysis and related approaches are significant tools based on calculating various physico-chemical properties and predicting biological activity, ADME parameters, and toxicity of a molecule. These methods are used to evaluate a molecule's potential to become a drug candidate. Avenanthramides (AVNs) are promising secondary metabolites specific to Avena spp. (oat). They comprise the amides of anthranilic acid linked to various polyphenolic acids with or without post-condensation molecule transformation. These natural compounds have been reported to exert numerous biological effects, including antioxidant, anti-inflammatory, hepatoprotective, antiatherogenic, and antiproliferative properties. To date, almost 50 various AVNs have been identified. We performed a modified POM analysis of 42 AVNs using MOLINSPIRATION, SWISSADME, and OSIRIS software. The evaluation of primary in silico parameters revealed significant differences among individual AVNs, highlighting the most promising candidates. These preliminary results may help coordinate and initiate other research projects focused on particular AVNs, especially those with predicted bioactivity, low toxicity, optimal ADME parameters, and promising perspectives.

In silico and POM analysis for potential antimicrobial agents of thymidine analogs by using molecular docking, molecular dynamics and ADMET profiling.

Nucleoside analogs are an important, well-established class of clinically useful medicinal agents that exhibit potent antimicrobial activity. Thus, we designed to explore the synthesis and spectral characterization of 5'-O-(myristoyl)thymidine esters (2-6) for in vitro antimicrobial, molecular docking, molecular dynamics, SAR, and POM analyses. An unimolar myristoylation of thymidine under controlled conditions furnished the 5'-O-(myristoyl)thymidine and it was further converted into four 3'-O-(acyl)-5'-O-(myristoyl)thymidine analogs. The chemical structures of the synthesized analogs were ascertained by analyzing their physicochemical, elemental, and spectroscopic data. In vitro antimicrobial tests along with PASS, prediction indicated expectant antibacterial functionality of these thymidine esters compared to the antifungal activities. In support of this observation, their molecular docking studies have been performed against lanosterol 14α-demethylase (CYP51A1) and Aspergillus flavus (1R51) and significant binding affinities and non-bonding interactions were observed. The stability of the protein-ligand complexes was monitored by a 100 ns MD simulation and found the stable conformation and binding mode in a stimulating environment of thymidine esters. Pharmacokinetic predictions were studied to assess their ADMET properties and showed promising results in silico. SAR investigation indicated that acyl chains, lauroyl (C-12) and myristoyl (C-14), combined with deoxyribose, were most effective against the tested bacterial and fungal pathogens. The POM analyses provide the structural features responsible for their combined antibacterial/antifungal activity and provide guidelines for further modifications, with the aim of improving each activity and selectivity of designed drugs targeting potentially drug-resistant microorganisms. It also opens avenues for the development of newer antimicrobial agents targeting bacterial and fungal pathogens.

A novel series of 5´-O-(myristoyl)thymidine derivatives were synthesized and characterized by FTIR, ¹H-NMR, 2D-NMR, ¹³C-NMR, mass and physicochemical studies.In vitro antimicrobial susceptibility revealed that alkyl chain and aromatic substituents can improve the antimicrobial efficacy of the thymidine structure which was also supported by PASS enumeration.Molecular docking study against lanosterol 14α-demethylase (CYP51A1) and Aspergillus flavus (1R51) exhibited a promising binding score and interaction in the catalytic active site.A 100ns MD simulation revealed the stable conformation and binding pattern in a stimulating environment of thymidine derivatives.ADMET analysis revealed that most of the compounds are non-toxic and most of them have an inhibitory property to the CYP1A2 and CYP3A4In silico and POM analyses provide substantial ideas about the structural features responsible for their combined antibacterial/antifungal agents and provide guidelines for further modifications.

A pair of carbazate derivatives as novel Schiff base ligands: DFT and POM theory supported spectroscopic and biological evaluation.

Schiff bases are mentioned as strongly important molecular scaffolds of industrial and medicinal purposes. Due to wide range applications of carbazate derivatives herein synthesis and characterization of a new Schiff base ligand, (E)-ethyl 2-(4-methoxybenzylidene)hydrazinecarboxylate and 4-(nitrobenzaldehyde)ethylcarbazate are reported. The compound was characterized on the basis of experimental and density functional theory calculations (using the B3LYP and 6-31 G(d,p)formalism combination). Among characterization techniques elemental analysis, FT-IR, UV-Vis and NMR spectroscopic evaluations were mainly employed to carry out the formulation of the compound. In addition to computational validation of characterization other significant molecular parameters were also evaluated including geometry optimization, frontier molecular orbital analysis (FMO) and Columbic interaction of different constituent atoms of the title compound. A good agreement has been found between DFT and experimental outcomes confined to prove the structure of the compound. Moreover, molecular docking and antimicrobial studies have proven the Schiff base as an effective bioactive compound.Communicated by Ramaswamy H. Sarma.

In silico evaluation of molecular interactions between macrocyclic inhibitors with the HCV NS3 protease. Docking and identification of antiviral pharmacophore site.

An array of computational approaches DFT/QSAR/POM methods has been used for a better understanding of drug properties regarding 13 inhibitor derivatives containing either P2 cyclopentane P1 carboxylic acid moiety (1-9) or a P1 cyclopropyl acyl sulfonamide (10-13). To further recognize binding interactions and their activity trends, molecular docking studies were carried out with the use of HCV, which can be used to accurately predict the interactions of ligands with the receptor. The QSAR models are developed through the use of Multiple Linear Regression (MLR) together with Principal Component Analysis (PCA) methods. The statistical results indicate the multiple correlation coefficient R2 = 0.840, which shows favorable estimation stability, as well as showing a significant correlation between the HCV NS3 protease of the studied compounds and their electron-accepting ability. The POM analysis of the Physico-chemical properties of compounds 1-13, shows that they are bearing (O1, O2) and/or (O1, O2, O3) antiviral pockets, whereby all oxygen atoms are Osp2 and bearing negative charges. Similar to the reference ligand (F9K), the most active compound 10 was bound deeply into the binding cavity of NS3 protease making interactions with the residues Gly137, His57, Ala157, and His528. The anti-hepatitis pharmacophore site is similar to the anti-HIV pharmacophore site.Communicated by Ramaswamy H. Sarma.

Drug design of new therapeutic agents: molecular docking, molecular dynamics simulation, DFT and POM analyses of new Schiff base ligands and impact of substituents on bioactivity of their potential antifungal pharmacophore site.

Since Schiff base derivatives have a wide range of biological activities, novel Schiff base derivatives were designed and synthesized in satisfactory yields. 1H NMR, 13C NMR, IR, mass and elemental analysis were used to provide a complete structural characterization of the new synthesized Schiff bases (3-6). The antiproliferative activity properties of compounds were tested against two human cancer cell lines including breast (MDA-MB-231) and colon (DLD-1). The compounds overall did not show high cytotoxic activity against both cancer cell lines compared to the positive control drug cisplatin. The synthesized Schiff base compounds were further screened for their in vitro antimicrobial activities against five bacterial strains (Escherichia coli (ATTC 25922), Salmonella thyphimurium (ATTC 14028), Staphylococcus aureus (ATCC 25923), Bacillus subtilis (ATCC 6633), Bacillus cereus (ATCC 11778)) and two fungal strains (Candida albicans (ATCC 10231) and Candida glabrata (ATCC 90030)) using broth micro dilution techniques. The mode of action for the antimicrobial effect in the experimental part was explored through molecular docking. The stability of target-ligand complexes obtained from the docking were assessed through molecular dynamics simulation. The binding affinity of the compounds toward the target protein were also investigated using MMPBSA. Furthermore, electrochemical properties of some compounds was analyzed by DFT calculations. By using POM theory, it becomes more easy to control the bioactivity of drugs. Here, how the physicochemical properties play a crucial role in the orientation of their bioactivity was demonstrated.Communicated by Ramaswamy H. Sarma.

Pheromone sensing in Drosophila requires support cell-expressed Osiris 8.

BACKGROUND: The nose of most animals comprises multiple sensory subsystems, which are defined by the expression of different olfactory receptor families. Drosophila melanogaster antennae contain two morphologically and functionally distinct subsystems that express odorant receptors (Ors) or ionotropic receptors (Irs). Although these receptors have been thoroughly characterized in this species, the subsystem-specific expression and roles of other genes are much less well-understood. RESULTS: Here we generate subsystem-specific transcriptomic datasets to identify hundreds of genes, encoding diverse protein classes, that are selectively enriched in either Or or Ir subsystems. Using single-cell antennal transcriptomic data and RNA in situ hybridization, we find that most neuronal genes-other than sensory receptor genes-are broadly expressed within the subsystems. By contrast, we identify many non-neuronal genes that exhibit highly selective expression, revealing substantial molecular heterogeneity in the non-neuronal cellular components of the olfactory subsystems. We characterize one Or subsystem-specific non-neuronal molecule, Osiris 8 (Osi8), a conserved member of a large, insect-specific family of transmembrane proteins. Osi8 is expressed in the membranes of tormogen support cells of pheromone-sensing trichoid sensilla. Loss of Osi8 does not have obvious impact on trichoid sensillar development or basal neuronal activity, but abolishes high sensitivity responses to pheromone ligands. CONCLUSIONS: This work identifies a new protein required for insect pheromone detection, emphasizes the importance of support cells in neuronal sensory functions, and provides a resource for future characterization of other olfactory subsystem-specific genes.

Crystallographic study, biological assessment and POM/Docking studies of pyrazoles-sulfonamide hybrids (PSH): Identification of a combined Antibacterial/Antiviral pharmacophore sites leading to in-silico screening the anti-Covid-19 activity.

The discovery and development of new potent antimicrobial and antioxidant agents is an essential lever to protect living beings against pathogenic microorganisms and free radicals. In this regard, new functionalized pyrazoles have been synthesized using a simple and accessible approach. The synthesized aminobenzoylpyrazoles 3a-h and pyrazole-sulfonamides 4a-g were obtained in good yields and were evaluated in vitro for their antimicrobial and antioxidant activities. The structures of the synthesized compounds were determined using IR, NMR, and mass spectrometry. The structure of the compound 4b was further confirmed by single crystal X-ray diffraction. The results of the in vitro screening show that the synthesized pyrazoles 3 and 4 exhibit a promising antimicrobial and antioxidant activities. Among the tested compounds, pyrazoles 3a, 3f, 4e, 4f, and 4g have exhibited remarkable antimicrobial activity against some microorganisms. In addition, compounds 3a, 3c, 3e, 4a, 4d, 4f, and 4g have shown a significant antioxidant activity in comparison with the standard butylhydroxytoluene (BHT). Hence, compounds 3a, 4f, and 4g represent interesting dual acting antimicrobial and antioxidant agents. In fact, pyrazole derivatives bearing sulfonamide moiety (4a-g) have displayed an important antimicrobial activity compared to pyrazoles 3a-h, this finding could be attributed to the synergistic effect of the pyrazole and sulfonamide pharmacophores. Furthermore, Molecular docking results revealed a good interaction of the synthesized compounds with the target proteins and provided important information about their interaction modes with the target enzyme. The results of the POM bioinformatics investigations (Petra, Osiris, Molinspiration) show that the studied heterocycles present a very good non toxicity profile, an excellent bioavailability, and pharmacokinetics. Finally, an antiviral pharmacophore (O δ-, O δ-) was evaluated in the POM investigations and deserves all our attention to be tested against Covid-19 and its Omicron and Delta mutants.

Biological activity of bis-(morpholineacetato)palladium(II) complex: Preparation, structural elucidation, cytotoxicity, DNA-/serum albumin-interaction, density functional theory, in-silico prediction and molecular modeling.

In an effort to discover a novel potential bioactive compound, a mono-nuclear Pd(II) complex with an amino acid derivative as ligand was synthesized and characterized through experimental and computational methodologies. A square-planar configuration was suggested for palladium(II) complex utilizing density functional theory. MEP map and Mulliken atomic charge were detected electrophilic and nucleophilic regions of the compound for reactions. The lipophilicity and cytotoxic activity of the complex was more effective than cisplatin. Also, OSIRIS DataWarrior revealed proper oral bioavailability and good drug-likeness for the compound. In-vitro binding behavior of the Pd(II) complex with DNA and serum albumin (BSA) were fully determined via variety of procedures including fluorescence, UV-Vis, CD, viscosity, gel electrophoresis experiments and molecular simulation. The negative signs of ΔH° and ΔS° for Pd(II) complex-CT-DNA/-BSA systems indicated the existence of hydrogen bonding/van der Waals interactions for both binding systems. Additionally, docking simulation illustrated the interaction of Pd(II) complex with the minor groove of DNA and the hydrophobic cavity of the BSA (drug binding site I).

Cross-Instrument Comparison of MapCam and OVIRS on OSIRIS-REx.

Two of the instruments onboard the OSIRIS-REx spacecraft, the MapCam color imager and the OVIRS visible and infrared spectrometer, observed the surface of asteroid (101955) Bennu in partially overlapping wavelengths. Significant scientific advances have been enabled by using data from these two instruments in tandem, but a robust statistical understanding of their relationship is needed for future analyses to cross-compare their data as accurately and sensitively as possible. Here we present a cross-instrument comparison of data acquired by MapCam and OVIRS, including methods and results for all global and site-specific observation campaigns in which both instruments were active. In our analysis, we consider both the absolute radiometric offset and the relative (normalized) variation between the two instruments; we find that both depend strongly on the photometric and instrumental conditions during the observation. The two instruments have a large absolute offset (>15%) due to their independent radiometric calibrations. However, they are very consistent (relative offset as low as 1%) when each instrument's response is normalized at a single wavelength, particularly at low phase angles where shadows on Bennu's rough surface are minimized. We recommend using the global datasets acquired at 12:30 pm local solar time for cross-comparisons; data acquired at higher phase angles have larger uncertainties.

CRISPR/Cas9 Targeted Editing of Osiris24 in Drosophlia melanogaster / 中国生物化学与分子生物学报

The gene expression of Osiris is coincident with the timing of chitin deposition. Osiris gene may be involved in the developmental regulation of insect cuticle. The objective of this study is to generate the gene-edited flies with Osiris24 by CRISPR/Cas9-mediated editing system to understand the traits of Osiris24 mutant flies and the expression pattern of Osiris24. Two sgRNA targeted sequences were designed according to the sequence of exon 1 of Osiris24 and inserted into pCFD4 vector backbone. A donor vector with Gal4 protein sequence was constructed. Above two plasmids were mixed and injected into nosCas9 fly embryos to generate GO generation. The results showed that 92.8% GO flies have Gal4 protein insert in genome. Homozygous mutants of Osiris24 were lethal at the embryonic stage or first-instar stage, and no visible phenotype was observed in heterozygous mutants. Osiris24 is expressed throughout larval and pupal stages. At the larval stage, Osiris24 is mainly expressed in the integument, foregut and hind-gut, while Osiris24 is expressed in the integument and wings at the pupal stage. These results indicated that Osiris24 plays an important role in the development of Drosophila. This study provides a research model for in-depth exploration of Osiris gene function.

How to face COVID-19: proposed treatments based on remdesivir and hydroxychloroquine in the presence of zinc sulfate. Docking/DFT/POM structural analysis.

Remdesivir and hydroxychloroquine derivatives form two important classes of heterocyclic compounds. They are known for their anti-malarial biological activity. This research aims to analyze the physicochemical properties of remdesivir and hydroxychloroquine compounds by the computational approach. DFT, docking, and POM analyses also identify antiviral pharmacophore sites of both compounds. The antiviral activity of hydroxychloroquine compound's in the presence of zinc sulfate and azithromycin is evaluated through its capacity to coordinate transition metals (M = Cu, Ni, Zn, Co, Ru, Pt). The obtained bioinformatic results showed the potent antiviral/antibacterial activity of the prepared mixture (Hydroxychloroquine/Azithromycin/Zinc sulfate) for all the opportunistic Gram-positive, Gram-negative in the presence of coronavirus compared with the complexes Polypyridine-Ruthenium-di-aquo. The postulated zinc(II) complex of hydroxychloroquine derivatives are indeed an effective antibacterial and antiviral agent against coronavirus and should be extended to other pathogens. The combination of a pharmacophore site with a redox [Metal(OH2)2] moiety is of crucial role to fight against viruses and bacteria strains. [Formula: see text]Communicated by Ramaswamy H. Sarma.

Antioxidant, Cytotoxic Activity and Pharmacokinetic Studies by Swiss Adme, Molinspiration, Osiris and DFT of PhTAD-substituted Dihydropyrrole Derivatives.

BACKGROUND: Pyrrole compounds having a heterocyclic structure are the most researched and biological activities such as antioxidant and anticancer activities. OBJECTIVE: Herein is a first effort to study the significance of heterocyclic compounds to include pyrrole and triazolidine-3,5-dion moiety, on the pharmacokinetic, antioxidant activity and cytotoxic activity on MCF-7 and MCF-12A cell lines. METHOD: The molecular structures of compounds I-XIV were simulated by the theoretical B3- LYP/DFT method. Pharmacokinetic studies of PhTAD-substituted heterocyclic compounds (IXIV) were analyzed to show Lipinski's rules via in-silico methods of Swiss-ADME. The drug likeness calculations were carried out in Molinspiration analyses. Some toxicity risk parameter can be quantified using Osiris. Antioxidant activities determined by DPPH, Fe+2 ions chelating and reducing. Cytotoxic activity measured by MTT and RTCA Results: Compared with the DPPH activity, the metal chelating activity exhibited serious similar antioxidant effects by PhTAD substituted pyrrole compounds. The same compounds showed the highest activity among the two antioxidant activities. The IC50 values of the compounds are in the range of 12 and 290 µM in the MCF-7 cell line. In the MTT and RTCA assays, All compounds showed cytotoxic activity, but about half of the fourteen compounds showed high cytotoxicity. IC50 values of the compounds are in the range of 5 and 54 µM for MTT and range of 1.5 and 44 µM for RTCA. CONCLUSION: Data of the antioxidant and cytotoxic activity of PhTAD-substituted dihydropyrrole- derived compounds in MCF-7 and MCF-12A cell lines confirmed that the compounds are biologically active compound and are notable for anti-cancer researches.

Distribution of variations in anatomy of the circle of Willis: results of a cadaveric study of the Malawian population and review of literature.

INTRODUCTION: the circle of Willis is an anatomical structure of clinical importance particularly in the evaluation of neurovascular diseases. Individuals show considerable variations in the anatomical configuration of the circle of Willis. A cross-sectional study was conducted to determine the distribution of morphological variations of the circle of Willis in Malawians and compare with other ethnic groups. METHODS: brains were collected from twenty-four recently deceased black Malawians during autopsy at Queen Elizabeth Central Hospital, a referral teaching hospital in Blantyre, Malawi and fixed in 10% buffered formalin. Digital images of the interpeduncular region (exposing the circle of Willis) were taken with an 18.4 megapixels camera from the base of the brain. Whole-circle and segmental parameters of the circle of Willis were assessed using the Osiris computer programme and classified based on a 22-type classification scheme. RESULTS: the following morphological variations were observed: hypoplasia, aplasia, asymmetry and accessory vessels. Typical circle of Willis was seen in 26% of the cases. Only six of the original twenty-two types were observed. Consistent with most previous studies, types 1, 3, 4, 6, 8 and 9 were common while types 10-22 were rare. Three variants not previously described in the original scheme (unilateral PcoA aplasia, AcoA duplication, and PcoA aplasia with contralateral PcoA hypoplasia) were observed in this study. CONCLUSION: anatomical variations of the circle of Willis in Malawians seem to be distributed in similar frequencies and patterns as in other more-diverse populations. Circle of Willis variants with potential predilection for atherogenesis and aneurysm formation exist in the Malawian population. These should be considered in clinical practice.

A Multi-target Drug Designing for BTK, MMP9, Proteasome and TAK1 for the Clinical Treatment of Mantle Cell Lymphoma.

BACKGROUND: Mantle cell lymphoma (MCL) is a type of non-Hodgkin lymphoma characterized by the mutation and overexpression of the cyclin D1 protein by the reciprocal chromosomal translocation t(11;14)(q13:q32). AIM: The present study aims to identify potential inhibition of MMP9, Proteasome, BTK, and TAK1 and determine the most suitable and effective protein target for the MCL. METHODOLOGY: Nine known inhibitors for MMP9, 24 for proteasome, 15 for BTK and 14 for TAK1 were screened. SB-3CT (PubChem ID: 9883002), oprozomib (PubChem ID: 25067547), zanubrutinib (PubChem ID: 135565884) and TAK1 inhibitor (PubChem ID: 66760355) were recognized as drugs with high binding capacity with their respective protein receptors. 41, 72, 102 and 3 virtual screened compounds were obtained after the similarity search with compound (PubChem ID:102173753), PubChem compound SCHEMBL15569297 (PubChem ID:72374403), PubChem compound SCHEMBL17075298 (PubChem ID:136970120) and compound CID: 71814473 with best virtual screened compounds. RESULT: MMP9 inhibitors show commendable affinity and good interaction profile of compound holding PubChem ID:102173753 over the most effective established inhibitor SB-3CT. The pharmacophore study of the best virtual screened compound reveals its high efficacy based on various interactions. The virtual screened compound's better affinity with the target MMP9 protein was deduced using toxicity and integration profile studies. CONCLUSION: Based on the ADMET profile, the compound (PubChem ID: 102173753) could be a potent drug for MCL treatment. Similar to the established SB-3CT, the compound was non-toxic with LD50 values for both the compounds lying in the same range.