Biological Evaluation Research Articles

Influence of bonding variance on electron affinity in graphene quantum dot-barium titanate nanocomposites for drug delivery system

Although chemotherapy remains a prevalent option in cancer treatment, its adverse effects on normal cells and suboptimal pharmacokinetics often limits its effectiveness. To address these challenges, this study successfully developed a new multifunctional drug delivery system comprising a covalent composite of graphene quantum dots and barium titanate nanoparticles. Notably, despite numerous reports on the surface modification of graphene quantum dots, studies focusing on cancer cell inhibition via different covalent bonds are scarce. To bridge this gap, this system was synthesized using eco-friendly esterification and amidation pathways. The anticancer drug doxorubicin was employed as a model drug, and hyaluronic acid was used to encapsulate the delivery system, enhancing its sustained release capabilities. Comprehensive material characterization confirmed the successful synthesis of the system. Its high drug loading capacity and acid-sensitive release can be attributed to the unique structure of the graphene quantum dots. Subsequent in vitro and in vivo biological evaluations not only demonstrated the system’s remarkable cancer inhibition efficacy but also accentuated the distinct impacts of the two bonding types. The underlying mechanism is believed to involve bonding affinity and electron transfer, findings that are corroborated by the experimental data. Additionally, results from animal models provide clear evidence for the potential application of this system (HA-DOX-GQD@BTNPs) in cancer therapeutics and imaging. In conclusion, this research elucidates the variances in drug carrier efficacy based on different covalent bond modifications for cancer treatment and introduces a novel drug delivery system that synergistically combines imaging and targeting capabilities.

In Vitro Biological Evaluation of an Alginate-Based Hydrogel Loaded with Rifampicin for Wound Care.

We report a biocompatible hydrogel dressing based on sodium alginate-grafted poly(N-vinylcaprolactam) prepared by encapsulation of Rifampicin as an antimicrobial drug and stabilizing the matrix through the repeated freeze-thawing method. The hydrogel structure and polymer-drug compatibility were confirmed by FTIR, and a series of hydrogen-bond-based interactions between alginate and Rifampicin were identified. A concentration of 0.69% Rifampicin was found in the polymeric matrix using HPLC analysis and spectrophotometric UV-Vis methods. The hydrogel's morphology was evaluated by scanning electron microscopy, and various sizes and shapes of pores, ranging from almost spherical geometries to irregular ones, with a smooth surface of the pore walls and high interconnectivity in the presence of the drug, were identified. The hydrogels are bioadhesive, and the adhesion strength increased after Rifampicin was encapsulated into the polymeric matrix, which suggests that these compositions are suitable for wound dressings. Antimicrobial activity against S. aureus and MRSA, with an increased effect in the presence of the drug, was also found in the newly prepared hydrogels. In vitro biological evaluation demonstrated the cytocompatibility of the hydrogels and their ability to stimulate cell multiplication and mutual cell communication. The in vitro scratch assay demonstrated the drug-loaded alginate-grafted poly(N-vinylcaprolactam) hydrogel's ability to stimulate cell migration and wound closure. All of these results suggest that the prepared hydrogels can be used as antimicrobial materials for wound healing and care applications.

Isatin-based ibuprofen and mefenamic acid Schiff base derivatives as dual inhibitors against urease and α–glucosidase: In vitro, in silico and cytotoxicity studies

α-Glucosidase and urease inhibitors have emerged as crucial for developing therapeutic drugs targeting diabetes and gastrointestinal disorders. This study reports on new series of ibuprofen and mefenamic acid Schiff base derivatives incorporating isatin as dual inhibitors of α-glucosidase and urease enzymes. These synthesized derivatives (7a-r) were structurally characterized by 1H NMR, 13C NMR and HRMS (EI). Biological evaluation (IC50) identified several derivatives i.e.,7a (urease = 17.37 ± 1.37 µM, α-glucosidase = 44.1 ± 1.15 µM), 7j, (urease = 16.61 ± 1.37 µM, α-glucosidase = 81.2 ± 1.33 µM), 7o, (urease = 18.63 ± 1.27 µM, α-glucosidase = 70.3 ± 1.14 µM), 7r (urease = 11.36 ± 1.32 µM, α-glucosidase = 39.3 ± 1.17 µM), as dual inhibitors of urease (thiourea 21.37 ± 1.76 µM) and α–glucosidase (acarbose 375.82 ± 1.76 µM) enzymes. These bioactive derivatives were explored for cell viability studies against mononuclear cells revealing a good cytocompatibility. In silico molecular docking studies were also conducted to predict the binding mode of new derivatives with target enzymes that were found consistent with the results of in vitro research.

Design, synthesis, and evaluation of benzodioxolane compounds for antitumor activity

This study reports the design, synthesis, and comprehensive biological evaluation of 13 benzodioxolane derivatives, derived from the core structure of piperine, a natural product with established antitumor properties. Piperine, primarily found in black pepper, has been noted for its diverse pharmacological activities, including anti-inflammatory, antioxidant, and anticancer effects. Leveraging piperine’s antitumor potential, we aimed to enhance its efficacy through structural modifications. Among the synthesized compounds, HJ1 emerged as the most potent, exhibiting a 4-fold and 10-fold increase in inhibitory effects on HeLa and MDA-MB-231 cell lines, respectively, compared to piperine. Furthermore, HJ1 demonstrated a favorable safety profile, characterized by significantly lower cytotoxicity towards the human normal cell line 293T. Mechanistic investigations revealed that HJ1 markedly inhibited clonogenicity, migration, and adhesion of HeLa cells. In vivo studies utilizing the chick embryo chorioallantoic membrane (CAM) model substantiated the robust antitumor activity of HJ1, evidenced by its ability to suppress tumor angiogenesis and reduce tumor weight. These results suggest that HJ1 holds significant promise as a lead compound for the development of novel antitumor therapies.

New 1,2,4-oxadiazole derivatives as potential multifunctional agents for the treatment of Alzheimer’s disease: design, synthesis, and biological evaluation

A series of new 1,2,4-oxadiazole-based derivatives were synthesized and evaluated for their anti-AD potential. The results revealed that eleven compounds (1b, 2a-c, 3b, 4a-c, and 5a-c) exhibited excellent inhibitory potential against AChE, with IC50 values ranging from 0.00098 to 0.07920 µM. Their potency was 1.55 to 125.47 times higher than that of donepezil (IC50 = 0.12297 µM). In contrast, the newly synthesized oxadiazole derivatives with IC50 values in the range of 16.64–70.82 µM exhibited less selectivity towards BuChE when compared to rivastigmine (IC50 = 5.88 µM). Moreover, oxadiazole derivative 2c (IC50 = 463.85 µM) was more potent antioxidant than quercetin (IC50 = 491.23 µM). Compounds 3b (IC50 = 536.83 µM) and 3c (IC50 = 582.44 µM) exhibited comparable antioxidant activity to that of quercetin. Oxadiazole derivatives 3b (IC50 = 140.02 µM) and 4c (IC50 = 117.43 µM) showed prominent MAO-B inhibitory potential. They were more potent than biperiden (IC50 = 237.59 µM). Compounds 1a, 1b, 3a, 3c, and 4b exhibited remarkable MAO-A inhibitory potential, with IC50 values ranging from 47.25 to 129.7 µM. Their potency was 1.1 to 3.03 times higher than that of methylene blue (IC50 = 143.6 µM). Most of the synthesized oxadiazole derivatives provided significant protection against induced HRBCs lysis, revealing the nontoxic effect of the synthesized compounds, thus making them safe drug candidates. The results unveiled oxadiazole derivatives 2b, 2c, 3b, 4a, 4c, and 5a as multitarget anti-AD agents. The high AChE inhibitory potential can be computationally explained by the synthesized oxadiazole derivatives’ significant interactions with the AChE active site. Compound 2b showed good physicochemical properties. All these data suggest that 2b could be considered as a promising candidate for future development.

Chemical Characterization and Biological Activities Evaluation of Myrtus communis L. Essential Oil Extraction By-Product towards Circular Economy and Sustainability.

Essential oil (EO) extraction is a widespread practice generating huge amounts of solid plant by-products a potential source of bioactive compounds, on the one hand, and a detrimental risk for the environment that needs to be carefully considered on the other hand. The present study aims to valorize Myrtus communis L. leaf by-products obtained following EO extraction using a steam distillation unit through the recovery of phenolic compounds and the evaluation of their biological activities. The total phenols, flavonoids, and proanthocyanidins contents of the ethanolic extract by-product were higher than the control (leaves without extraction of EO). Their amounts increased from 69.30 to 88.06 mg GAE/g for total phenols, from 36.31 to 70.97 mg QE for flavonoids and from 19.74 to 21.49 mg CE/g of extract for proanthocyanidins. The identification of phenolic compounds by high-performance liquid-chromatography equipped with a reversed-phase (RP-HPLC) system revealed that the by-product sample includes more gallic acid, catechin, syringic acid and luteolin 7-O-glucoside but less p-coumaric acid and kaempferol than the control. Moreover, the mid-infrared spectroscopy (MIR) showed the presence of benzene ring characteristic of phenolic compounds at 756 cm-1, esters of aromatic acids and stretching vibrations of polyphenols at 1141-1234 cm-1, C=C stretching present in phenolic acids such as coumaric acid and catechin at 1604 cm-1. The assessment of antioxidant activity revealed that the ABTS+• radical scavenging activity was significantly increased, whereas the DPPH• radical inhibition activity and the ferric reduction antioxidant power were significantly decreased. The results indicated, as well, that Myrtus communis L. leaf by-products maintained a considerable antibacterial activity depending on the tested bacterial strain. Additionally, the anti-α-amylase activity was higher for the Myrtus communis L. leaf by-product extract. Therefore, Myrtus communis L. leaf by-products of EO extraction offer phenolic compounds with significant biological activities, contributing to the sustainable development and the promotion of circular economy by the recovery of valuable inputs from plant by-products.

Quinazoline-oxindole hybrids as angiokinase inhibitors and anticancer agents: Design, synthesis, biological evaluation, and molecular docking studies.

Two new sets of quinazoline-oxindole 8a-l and quinazoline-dioxoisoindoline 10a-d hybrids were designed as type II angiokinase inhibitors and anticancer agents. The design strategy was adjusted to account for the quinazoline scaffold's placement in the target kinases' hinge region, where it would form hydrogen bonding and hydrophobic interactions with the important amino acids to stabilize it, and the amide group's occupation in the gate region, which would direct the oxindole scaffold toward the hydrophobic back pocket. The two sets of quinazolines 8a-l and 10a-d displayed pronounced inhibitory activity on VEGFR-2 (IC50 = 0.46-2.20 µM). The quinazoline-oxindole hybrids 8d, 8f, and 8h displayed IC50 = 0.46, 0.49, and 0.49 µM, respectively. Compound 8f demonstrated potent multikinase activity with IC50 values of 0.95 and 0.67 µM against FGFR-1 and BRAF, respectively. Additionally, compound 8f showed significant anticancer activity against National Cancer Institute's cancer cell lines, with GI50 reaching 1.21 µM. Analysis of the impact of compound 8f on the MDA-MB-231 cell line's cell cycle and apoptosis revealed that 8f stalled the cell cycle at the G2/M phase and promoted its necrosis.

Floral biology and agronomic evaluation of three hybrids of Portulaca umbraticola (Portulacaceae)

Floral biology and agronomic evaluation of three hybrids of Portulaca umbraticola (Portulacaceae)

Understanding the Regulatory Pathways Used to Develop, Evaluate, Authorize, and Approve New Drugs and Vaccines in the United States.

The United States (U.S.) Food and Drug Administration (FDA) oversees the safety and quality of drugs and vaccines that are used in the U.S. Administration of the FDA falls under the jurisdiction of the U.S. Department of Health and Human Services (HHS). The regulatory oversight of the FDA is complex and comprehensive, requiring the various roles and responsibilities to be divided across six main centers. The activities of two of these centers, the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) are the primary focus of this review.

The Development of a Highly Potent and Selective Human Toll-like Receptor 2 Agonist: Synthesis and Biological Evaluation of CaLGL-1 and Its Derivatives.

Toll-like receptor 2 (TLR2) plays a crucial role in detecting microbial pathogen-associated molecular patterns, offering potential applications as an adjuvant for vaccines and antitumor therapies. Here, we present the gram-scale synthesis of CaLGL-1 and its derivatives, natural products known for activating mouse TLR2 (EC50 = 3.2 μM). This synthesis involves a streamlined six-step reaction sequence utilizing oxidant-promoted acetalization, effectively preserving the acid-sensitive glycosidic bond for maintaining the compounds' functional integrity. Our structure-activity relationship studies identified R-7d as a potent human TLR2 activator. It demonstrated subnanomolar activity (EC50 = 116 pM) in human THP-1 cells, comparable to that of diprovocim (EC50 = 110 pM). Experiments revealed that R-7d enhances NF-kB promoter activation through TLR2/TLR1 heterodimers rather than TLR2/TLR6. The discovery of R-7d as a robust human TLR2 agonist opens up new possibilities for combination therapies.

Unveiling piperazine-quinoline hybrids as potential multi-target directed anti-Alzheimer's agents: design, synthesis and biological evaluation.

Multi-target directed ligands (MTDLs) have recently been popularized due to their outstanding efficacy in combating the complicated features of Alzheimer's disease. This study details the synthesis of piperazine-quinoline-based MTDLs through a multicomponent Petasis reaction, targeting multiple factors such as AChE, BuChE, metal chelation to restore metal dyshomeostasis, and antioxidant activity. Some of the synthesized compounds exhibited notable inhibitory activity against AChE and BuChE enzymes at specific concentrations. Among the synthesized compounds compound (95) containing a 4-chloroaniline moiety and a 4-methoxybenzyl group displayed the most promising inhibitory activities against AChE (IC50 3.013 µM) and BuChE (IC50 = 3.144 µM). Compound (83) featuring 2-methoxyaniline and 4-fluorobenzyl substituents, exhibited the highest BuChE inhibition (IC50 1.888 µM). Notably, compound (79) demonstrated 93-times higher selectivity for BuChE over AChE. Molecular docking and molecular dynamics simulations were also performed to explore the binding modes and stability of these compounds with the AChE amd BuChE proteins. Further, kinetics study was performed against AChE for comounds (83 and 95) which indicated mixed inhibition of the enzyme by these compounds, Amongs the synthesized compounds, nine compounds were assessed for their antioxidant activity, displaying significant antioxidant properties with IC50 values ranging from 156 µM to 310 µM. Moreover, all the compounds demonstrated metal chelating tendency with Cu+2, Zn+2, Fe+2, Fe+3 and Al+3. This study provides insights into the design of novel MTDLs, highlighting compound (95) as a potential candidate for combating Alzheimer's disease.

Identification of potential natural product derivatives as CK2 inhibitors based on GA-MLR QSAR modeling, synthesis and biological evaluation

Identification of potential natural product derivatives as CK2 inhibitors based on GA-MLR QSAR modeling, synthesis and biological evaluation

2-(Piperidin-3-yl)phthalimides reduce classical markers of cellular inflammation in LPS-challenged RAW 264.7 cells and also demonstrate potentially relevant sigma and serotonin receptor affinity in membrane preparations

Herein, we report the synthesis of new 4-amino-2-(piperidin-3-yl)isoindoline-1,3-diones and their biological evaluation in a series of in vitro experiments. The synthetic production of these materials was initiated upon the condensation of appropriate nitrophthalic acid derivatives with various 3-aminopiperidines; subsequent reduction provided the final products in moderate to good yields. Readily available chiral pool reagents facilitated entry into optically enriched samples, while the piperidine scaffold furnished a variety of amide and alkylated entries. In total, 16 candidates were produced, and their ensuing treatment in LPS-challenged RAW cells effected slight reductions in secreted TNF-α but provided more robust and dose-dependent declines in nitrite and IL-6 levels relative to basal amounts, all concurrent with maintenance of cellular viability across the concentration ranges screened. The secondary amine cohort including rac-6, (R)-7, and (S)-8 rendered the most pronounced dose-dependent reductions in nitrite and IL-6. When dosed at 30 μM, (R)-7 demonstrated the most compelling effects, with decreases of 32 % and 40 % for nitrite and IL-6, respectively. Notable reductions in the inflammatory markers were also observed for 19 which effected declines in TNF-α (14 %), nitrite (19 %), and IL-6 (11 %) when treated at 30 μM. Additionally, four representative compounds were further evaluated against numerous CNS receptors, channels, and transporters, with 6, 9, and 19 demonstrating varying degrees of nanomolar-to-low-micromolar binding to the σ-1 and σ-2 receptors and also to serotonin receptors 5HT2A, 5HT2B and 5HT3. In this regard, 6 displayed perhaps the most noteworthy affinities, with binding at σ-2 (Ki = 2.2uM), 5HT2B (Ki = 561 nM) and 5HT3 (Ki = 536 nM). Furthermore, no pronounced or dose-dependent Cereblon/DDB1 binding was observed for the screened representative compounds 6, 9, 18 and 19.

Design, synthesis and biological Evaluation of novel chromones having 3,4-dihydropyrimidin-2(1H)-one core at C-8 in combination with triazoles: New α-glucosidase inhibitors and anti-bacterial agents

The Biginelli reaction synthesizes dihydropyrimidones through a multi-component reaction. A β-ketoester, aldehyde, and urea or thiourea react in the presence of an acid catalyst to form these dihydropyrimidones. 3,4-Dihydropyrimidin-2(1H)-One/Chromone/Triazole hybrids (9a-9l) were synthesized by multiple steps including one pot Biginelli multicomponent reaction depicted in the scheme. An efficient method for the Biginelli reaction of Chromone aldehyde, acetoacetate esters, and urea employed in the presence of ferric chloride is described. In the end, we have successfully synthesized twelve derivatives of 3,4-Dihydropyrimidin-2(1H)-One/Chromone/Triazole hybrids and subjected them to testing for Antibacterial activity and α-glucosidase inhibition activity. Among these derivatives, compound 9g (IC50 = 142.92 nmol) and 9e (144.49 nmol) exhibited significant inhibitory activity in comparison to the positive control acarbose (IC50 = 350.91 nmol). Compound 9g demonstrated the most significant suppression against Escherichia coli and Bacillus cereus, with zone diameters of 8.8 ± 1.35 mm and 9.1 ± 0.23 mm, respectively. Compound 9b displayed a clear area where bacterial growth was inhibited, measuring 7.5 ± 1.25 mm against Klebsiella pneumonia. Compound 9k exhibited a zone of inhibition measuring 8 ± 1.2 mm in radius against Staphylococcus epidermidis. The docking results for the synthesized compounds indicate that compound 9b exhibited the most favorable docking score of −10 kcal/mol, whereas compound 9a had the second-best docking score of −8.7 kcal/mol. Molecular docking was utilized to examine the interactions between the title compounds and α-glucosidase, in order to provide valuable insights. The data obtained revealed significant interactions that contribute to the inhibitory effects of the drugs against α-glucosidase. These compounds exhibit significant potential as attractive initial candidates for the development of new α-glucosidase inhibitors.

Synthesis and Biological Evaluation of Novel 2-Aroyl Benzofuran-Based Hydroxamic Acids as Antimicrotubule Agents.

Because of synergism between tubulin and HDAC inhibitors, we used the pharmacophore fusion strategy to generate potential tubulin-HDAC dual inhibitors. Drug design was based on the introduction of a N-hydroxyacrylamide or a N-hydroxypropiolamide at the 5-position of the 2-aroylbenzo[b]furan skeleton, to produce compounds 6a-i and 11a-h, respectively. Among the synthesized compounds, derivatives 6a, 6c, 6e, 6g, 11a, and 11c showed excellent antiproliferative activity, with IC50 values at single- or double-digit nanomolar levels, against the A549, HT-29, and MCF-7 cells resistant towards the control compound combretastatin A-4 (CA-4). Compounds 11a and 6g were also 10-fold more active than CA-4 against the Hela cell line. When comparing the inhibition of tubulin polymerization versus the HDAC6 inhibitory activity, we found that 6a-g, 6i, 11a, 11c, and 11e, although very potent as inhibitors of tubulin assembly, did not have significant inhibitory activity against HDAC6.

Design and bio-evaluation of novel millepachine derivatives targeting tubulin colchicine binding site for treatment of osteosarcoma

Microtubules are recognized as an appealing target for cancer treatment. We designed and synthesized of novel tubulin colchicine binding site inhibitors based on millepachine. Biological evaluation revealed compound 5h exhibited significant antiproliferative activity against osteosarcoma cell U2OS and MG-63. And compound 5h also remarkably inhibited tubulin polymerization. Further investigations indicated compound 5h not only arrest U2OS cells cycle at the G2/M phases, but also induced U2OS cells apoptosis in dose-dependent manners. Moreover, compound 5h was verified to inhibit cell migration and angiogenesis of HUVECs, induce mitochondrial membrane potential decreased and promoted the elevation of ROS levels. Furthermore, compound 5h exhibited remarkable effects on tumor growth in vivo, and the TGI rate was up to 84.94 % at a dose of 20 mg/kg without obvious toxicity. These results indicated that 5h may be an appealing tubulin inhibitor for treatment of osteosarcoma.

Development of a porcine decellularized extracellular matrix (DECM) bioink for 3D bioprinting of meniscus tissue engineering: formulation, characterisation and biological evaluation

ABSTRACT This study aims to present an easily scalable, cost-efficient process of dECM extraction from porcine meniscus, dedicated to bioink preparation and 3D bioprinting. Due to its cartilage like structure and mechanical robustness, the meniscus is an exceptionally demanding tissue for extraction and decellularisation of its ECM. Its processing poses a great difficulty and renders the methods previously developed for soft tissues useless. A process, combining homogenisation, hydrolysis, supercritical CO2 (scCO2) extraction and lyophilisation, was developed to meet this challenge. This protocol allows for retaining its native compounds and biocompatibility while offering good printability and providing a stimulatory environment for cell proliferation and differentiation towards a meniscus-like phenotype. Also, this process is economically and ecologically friendly since it doesn't require the use of high amounts of solvents, detergents or expensive enzymes (DNase). The decellularisation process has been meticulously studied, demonstrating a substantial reduction in DNA content but still exceeding accepted thresholds. The study further explores the biocompatibility of the dECM, demonstrating no detrimental effects of remnant DNA on cell survival during extended in vitro culture, indicating excellent biocompatibility. These findings challenge the current definition of decellularisation effectiveness based solely on DNA content, proposing a broader assessment of biological effects.

Biological and Mechanical Evaluation of Integrated Nano-Hydroxyapatite in 3D-Printed Polylactic Acid Scaffold

Biological and Mechanical Evaluation of Integrated Nano-Hydroxyapatite in 3D-Printed Polylactic Acid Scaffold

Synthesis and biological evaluation of novel isoxazoloquinone derivatives as potent STAT3-targeting antipsoriasis agents

Psoriasis is a troublesome scaling skin disease with no high-effective medication available by far. Signal transducer and activator of transcription 3 (STAT3) has recently been revealed as a crucial player in the pathogenesis and progression of psoriasis and emerged as an intriguing antipsoriatic drug target. Naturally occurring lapachol and its quinone analogs had been discovered as effective STAT3 inhibitors, however, their antipsoriatic effects are not well investigated. Previously, we have reported a series of isothiazoloquinone lapachol derivatives. Here, the antipsoriastic potentials of these isothiazoloquinones were investigated and, in addition, 35 novel isoxazoloquinone derivatives were prepared and studied for their anti-psoriasis properties. Among them, the most potent antipsoriatic compound B20 determined by in vitro test on HaCaT cells could directly bind to STAT3, reduce STAT3 level and inhibit STAT3 nuclear translocation. In vivo studies showed that topical application of B20 could effectively alleviate IMQ-induced psoriasis in mice with no obvious side effects. In addition, B20 inhibited the production of interleukin 17 (IL-17A), a STAT3-downstream cytokine essential for the progression of psoriasis, both in vitro and in vivo. Thus, isoxazoloquinone B20 is a potent STAT3-targeting antipsoriatic agent worth of further investigation.

Exploring novel bromo heterocyclic scaffold and theoretical explanation of their biological actions

In this elucidation, we synthesized different heterocyclic compounds through (E)-1-(2‑bromo-4-methylphenyl)-3-(4-bromophenyl)prop‑2-en-1-one(3) which is synthesized from the aldol condensation between 4-bromobenzaldehyde and 1-(2‑bromo-4-methylphenyl)ethan-1-one in the basic condition in excellent yield. Furthermore, the chalcone 3 showed also varied activity with nitrogen nucleophiles and active methylene and displayed different heterocyclic rings which were confirmed through different spectral analyses such as FT-IR, 1HNMR, 13CNMR, and mass spectrum. Moreover, the synthesized heterocyclic exhibited antimicrobial properties against various microbial strains (Gram-positive, Gram-negative, and fungal strains) through the well diffusion methodology and comparable with Ampicillin and Mycostatin drugs. Furthermore, the synthesized compounds demonstrated various radical scavenger properties and antioxidant activities. These biological analyses demonstrated various binding energies and interactions with proteins and were validated through molecular docking studies using distinct protein pockets interaction. Additionally, the Frontier Molecular Orbitals (FMO), which are physical descriptors of optimal structures that are connected with biological evaluations and demonstrate the activities of these compounds due to presence of two bromine atom which effect on electron deficiency and increase its action which examined via the DFT/B3LYP/6-311G basis set.