Immunohistochemical Expression of CXCL 10 in Vitiligo.

BACKGROUND: Vitiligo is a skin disorder characterized by the loss of melanocytes from the epidermis. Cysteine x cysteine motif chemokine ligand 10 (CXCL10) is linked to the Th1 pattern and has been suggested as one of the most relevant chemokine axes that promote T-cell migration in different autoimmune and inflammatory processes. The aim of this study was to assess the immunohistochemical (IHC) expression of CXCL 10 in skin lesions of patients with vitiligo to explore its possible role in the pathogenesis of the disease. METHODS: In this prospective, case-control study, we examined biopsies from the lesional skin of 20 patients with vitiligo for IHC expression of CXCL 10: 10 patients presented with stable nonsegmental vitiligo (group A), 10 patients presented with active nonsegmental vitiligo (group B), and 10 apparently healthy volunteers were examined as controls (group C). RESULTS: Nine patients in group A had mild IHC expression of CXCL 10 (+1) and 1 patient had moderate expression (+2). In group B, 8 patients had strong expression of CXCL 10 (+3), and the remaining patients had moderate expression (+2). However, there was no expression of CXCL 10 in all skin specimens in the control group. CONCLUSIONS: CXCL10 IHC expression was increased in vitiligo lesions indicating a possible role in the pathogenesis of disease. The expression was significantly increased in active vitiligo compared with stable vitiligo.

Removal of black tattoos by Picosecond Q-switched Nd-YAG laser in the middle eastern skin type IV: prospective study.

Tattoo removal is considered a challenging field in cosmetic dermatology. Picosecond Q-switched Nd-YAG lasers targeting unique chromophores effectively manage this condition without serious complications. To evaluate the efficacy and safety of Picosecond Q-switched Nd-YAG laser in the treatment of black tattoos in the skin of middle eastern mostly skin type IV. The study was carried out on 20 patients with skin type IV the most common in middle eastern area with professional black tattoos. They were treated by Picosecond Nd-YAG laser (2 sessions 8 weeks apart). The percentage of improvement ranged from 20.0 to 95.0 (with a mean of 61 ± 24.6). 8 patients (40%) showed excellent improvement, 4 patients (20%) showed marked improvement, 4 patients (20%) showed moderate improvement, and 4 patients (20%) showed mild improvement. No severe side effects were detected. Picosecond Nd-YAG laser was an effective and safe technique in the treatment of professional black tattoos; with only 2 sessions most patients reached excellent to moderate response with minimal side effects.

Balancing confidentiality and care coordination: challenges in patient privacy.

BACKGROUND: In the digital age, maintaining patient confidentiality while ensuring effective care coordination poses significant challenges for healthcare providers, particularly nurses. AIM: To investigate the challenges and strategies associated with balancing patient confidentiality and effective care coordination in the digital age. METHODS: A cross-sectional study was conducted in a general hospital in Egypt to collect data from 150 nurses across various departments with at least six months of experience in patient care. Data were collected using six tools: Demographic Form, HIPAA Compliance Checklist, Privacy Impact Assessment (PIA) Tool, Data Sharing Agreement (DSA) Framework, EHR Privacy and Security Assessment Tool, and NIST Cybersecurity Framework. Validity and Reliability were ensured through pilot testing and factor analysis. RESULTS: Participants were primarily aged 31-40 years (45%), with 75% female and 60% staff nurses. High compliance was observed in the HIPAA Compliance Checklist, especially in Administrative Safeguards (3.8 ± 0.5), indicating strong management and training processes, with an overall score of 85 ± 10. The PIA Tool showed robust privacy management, with Project Descriptions scoring 4.5 ± 0.3 and a total score of 30 ± 3. The DSA Framework had a mean total score of 20 ± 2, with Data Protection Measures scoring highest at 4.0 ± 0.4. The EHR assessments revealed high scores in Access Controls (4.4 ± 0.3) and Data Integrity Measures (4.3 ± 0.3), with an overall score of 22 ± 1.5. The NIST Cybersecurity Framework had a total score of 18 ± 2, with the highest scores in Protect (3.8) and lower in Detect (3.6). Strong positive correlations were found between HIPAA Compliance and EHR Privacy (r = 0.70, p < 0.05) and NIST Cybersecurity (r = 0.55, p < 0.05), reflecting effective data protection practices. CONCLUSION: The study suggests that continuous improvement in privacy practices among healthcare providers, through ongoing training and comprehensive privacy frameworks, is vital for enhancing patient confidentiality and supporting effective care coordination.

CD154 Resistant to Cleavage from Intracellular Milieu and Cell Surface Induces More Potent CD40-Mediated Responses.

In addition to the membrane-bound form, CD154 also exists as a soluble molecule originating from an intracellular and membrane cleavage. We have previously shown that CD154 cleavage from T cell surface is mediated by CD40 and involves the action of ADAM10/ADAM17 enzymes. In the aim of defining the importance of CD154 maintained on cell surface, we generated a CD154 mutated at the cleavage site. Our data show that the double mutation of E112 and M113 residues of CD154 abolishes its spontaneous release and the CD40-mediated cleavage from cell surface but does not affect its binding to CD40. We also demonstrated that both the release of CD154 from the intracellular milieu and its CD40-mediated cleavage from cell surface are highly dependent on ADAM10/ADAM17 enzymes. The CD154-EM mutant was shown capable of inducing a more prominent apoptotic response in susceptible B cell lines than the wild-type (WT) form of the molecule. In addition, human B cells cultured in the presence of the CD154-EM mutant exhibited upregulated proliferative responses compared with the CD154-WT. The CD154-EM mutant was also shown to trigger differentiation of human B cells, reflected by an increased Ig production, more significantly than CD154-WT. Thus, our data strongly suggest that cleavage-resistant CD154 is a more prominent stimulant than the cleavable form of the molecule. Therefore, a maintained expression of CD154 on cell membrane and a disturbed cleavage of the molecule could be a mechanism by which CD154 is involved in some pathological conditions and should be revisited.

New tilomisole-based benzimidazothiazole derivatives as anti-inflammatory agents: Synthesis, in vivo, in vitro evaluation, and in silico studies.

New tilomisole-based benzimidazothiazole derivatives were designed and synthesized in this work. Their anti-inflammatory activity was assessed through the in vivo carrageenan rat paw edema model, and the in vitro COX inhibition assay. Compounds 13, 20, 30, 40, 43, and 46 demonstrated values of inhibition of induced edema in the in vivo assay comparable to celecoxib. All the synthesized compounds expressed their activity on COX-2 enzyme more than COX-1, proving their advantageous selectivity. In addition, compounds 13, 16, 20, 25, and 46 displayed lower IC50 values than celecoxib as a reference drug against COX-2 enzyme; having values of 0.09, 13.87, 32.28, 33.01, and 5.18 nM respectively vs 40.00 nM for celecoxib. Particularly, the most active compound (13) with its extreme potency (400 folds more potent than celecoxib) exhibited a notable high selectivity index (SI = 159.5). In silico studies, including ADMET prediction, compliance to Lipinski's rule of five, and molecular docking into the active site of both COX isozymes were conducted for the synthesized compounds. The results suggested that these compounds are good candidates for orally active drugs, and docking revealed higher number of interactions with COX-2 for 13 as the most active compound compared with COX-1 reflecting its advantageous selectivity and explaining its extreme potency.

Facial rejuvenation by microneedling with irradiated amniotic collagen matrix compared to platelet rich plasma.

Many modalities are used for treatment of facial wrinkles, such as microneedling that enhances collagen production, and platelet-rich plasma (PRP) which contains concentrated levels of growth factors. The human amniotic membrane isolated from the placentae of donors (during elective cesarean sections) has high levels of growth factors that help in rejuvenation by improving the migration and proliferation of keratinocytes, fibroblasts and increased collagen synthesis. Was to confirm the efficacy of irradiated amniotic collagen matrix (IACM) versus platelet rich plasma (PRP) delivered via microneedling in facial rejuvenation. The present study included 20 patients with facial wrinkles divided into two groups using split face technique: Group A subjected to microneedling with topical IACM on the right side of the face. Group B subjected to microneedling with topical PRP on the left side of the face. Patients received six sessions 2 weeks apart. Photos by Antera camera and skin biopsies were taken to assess the clinical results. There were a statistically significant improvement in both sides after than before treatment; with better improvement in patients treated with IACM more than patients treated with PRP using microneedling in both sides as proved clinically (assessed by WSRS and GAIS scale), pathologically (Orcein and Masson trichrome stain) and by Antera camera (texture and pigmentation). Microneedling using IACM is a new, safe and effective method for facial rejuvenation, more effective when compared to microneedling using PRP; in need for further studies to evaluate the correct dose and number of sessions to get the best outcome.

Evaluation of the efficacy and safety of platelet rich plasma injection in treatment of rosacea.

Rosacea is a chronic relapsing inflammatory skin disease, with a high prevalence among adults. Treatment of rosacea is difficult, with high rate of recurrence. Due to the strong anti- inflammatory and antibacterial effects of platelet rich plasma (PRP), it was used in the medicine for treating many inflammatory diseases. To evaluate the role of PRP injection in treatment of rosacea. The study was carried on 40 patients with rosacea. They were treated by PRP injection in right side of the face (group A) and platelet poor plasma injection in left side (group B). They underwent one session every 2 weeks for 3 months (6 sessions). The patients were assessed clinically before and after treatment by the rosacea grading scale. Skin biopsies were taken to evaluate the clinical results. There was a statistically significant decrease in rosacea grading scale after treatment with PRP injection, 50% of the patients showed excellent improvement and 50% showed good improvement. The improvement was significantly better in group A than B. There was marked decrease in inflammatory cells by hematoxylin and eosin stain, and decrease in expression of nuclear factor kappa ßeta after treatment with PRP. PRP was effective and safe technique in treatment of rosacea and alternative to other systemic modalities, especially if they are contraindicated.

New thiazolopyrimidine as anticancer agents: Synthesis, biological evaluation, DNA binding, molecular modeling and ADMET study.

In the present study, new series of thiazolopyrimidine derivatives was synthesized as purine analogs. The structures of the products were confirmed through spectroscopic techniques such as NMR and mass spectrometry. In addition, the synthesized compounds were evaluated as antitumor active agent through NCI screening protocol against 60 different cell lines under 9 different panels. Furthermore, DNA binding activity of the compounds was also evaluated. The results revealed that compound 35 proved to be the most active member of the tested series and it is promoted to the 5-dose testing where it gives GI50, TGI and LC50 values of 1.07, 6.61, 34.7 µM respectively. Furthermore, it also proved to have a good DNA binding activity with value that is comparable with that produced by doxorubicin which was used as positive standard. In addition, compound 27 was proved to be the most active DNA binding agent with binding affinity 28.38 ± 1.1. The pharmacokinetic properties were also calculated. Molecular docking studies suggested binding mode of compounds 27 and 35 to DNA minor groove via hydrogen bonding interaction. The anticancer activity of compounds 27 and 35 may be attributed to DNA binding.

Targeting EGFR tyrosine kinase: Synthesis, in vitro antitumor evaluation, and molecular modeling studies of benzothiazole-based derivatives.

New benzothiazole-based derivatives were synthesized in the present work with the aim of evaluating their antitumor activity. They were in vitro tested against hepatocellular carcinoma (HepG2), colorectal carcinoma (HCT-116), mammary gland cancer (MCF-7), prostate cancer (PC-3), and epithelioid carcinoma (HeLa). The results of the in vitro antitumor evaluation revealed that the most active compounds were 39, 40, 51, 56, and 61 exhibiting IC50 values comparable to the reference drug lapatinib. The most active compounds were further subjected to EGFR inhibitory activity assay to rationalize their potency mode. Notably, the most active antitumor compounds 39 and 40 represented the most potent inhibitors to EGFR with IC50 values of 24.58 and 30.42 nM respectively in comparison with 17.38 nM for lapatinib as a standard drug. Molecular modeling studies were also conducted for the synthesized compounds, including docking into EGFR active site and surface mapping. Results proved the superior binding of the hydrazone derivatives 39 and 40 with EGFR suggesting them as good candidates for targeted antitumor therapy through EGFR kinase inhibition.

DNA binding studies of novel diazatruxenones analogs as potential anticancer agents: Synthesis, antitumor investigation, DNA binding, SAR and molecular modeling calculation.

A series of polycyclic skeleton of truxene and triazatruxene analogs has been synthesized and evaluated for antitumor and DNA binding activities. The synthesized structures were confirmed by different spectroscopic techniques such as IR, 1HNMR, 13CNMR, and mass spectroscopy. The antitumor screening was performed adopting the NCI protocol against 60 different cell lines. Compounds 2 and 8 proved to be the most active ones among the other target compounds. In a trial to investigate the mechanism of action of the target compounds, DNA binding activity was also investigated. Compounds 3f, 4-8 exhibited good binding activity explaining their mechanism. In addition, molecular modeling studies were also performed for more clearance of the data obtained from the biological screening.

Safety and efficacy of platelet-rich plasma vs carboxytherapy in the treatment of atrophic scars: A comparative clinical and histopathological study.

Atrophic scars that occur after surgical procedure or trauma are considered as a cosmetic problem for patients. Atrophic scarring results usually during wound healing with inadequate production of collagen and connective tissue. Factors that precipitate to the formation of depressed scars include: individual variations in wound healing, wound tension, tissue apposition, and scar contraction. To evaluate the safety and efficacy of PRP vs carboxytherapy in treatment of atrophic scars. This study included 40 patients with atrophic scars divided into two groups; group A including 20 patients received PRP injection, group B including 20 patients received CO2 injection. They received the treatment every 4 weeks for four sessions and had follow up for 6 months after the end of treatment. Skin biopsies were taken before and after treatment to evaluate clinical results. There was statistically significant difference between both groups in treating atrophic scars, regarding clinical improvement and patients' satisfaction with better results in group B. Histopathological examination showed significant expression of MMP-1 in group B more than group A. Both methods were safe and effective with minimal side effects with better improvement in patients treated with carboxytherapy than those treated with PRP.

Antitumor properties of certain spirooxindoles towards hepatocellular carcinoma endowed with antioxidant activity.

In the current medical era, spirooxindole motif stands out as a privileged heterospirocyclic scaffold that represents the core for a wide range of bioactive naturally isolated products (such as Strychnofoline and spirotryprostatins A and B) and synthetic compounds. Interestingly, no much attention has been paid to develop spirooxindole derivatives with dual antioxidant and anticancer activities. In this context, a series of spirooxindoles 6a-p was examined for their anticancer effect towards HepG2 hepatocellular carcinoma and PC-3 prostate cancer cell lines. Spirooxindole 6a was found to be an efficient anti-proliferative agent towards both HepG2 and PC-3 cells (IC50 = 6.9 and 11.8 µM, respectively). Afterwards, spirooxindole 6a was assessed for its apoptosis induction potential in HepG2 cells, where its pro-apoptotic impact was approved via the significant elevation in the Bax/Bcl-2 ratio and the expression levels of caspase-3.

The efficacy of radiofrequency, intense pulsed light and carboxytherapy in facial rejuvenation.

Skin aging may be divided into intrinsic and extrinsic aging or photoaging. The first is a natural, slow and gradual process. The second is exacerbated by environmental factors such as improper exposure to sunlight. There are a myriad of therapeutic modalities that can improve photoaging. Intense pulsed light, radiofrequency and carboxytherapy are good procedural modalities to improve skin aging. This study aimed to evaluate and compare the efficacy and safety of IPL, RF, and carboxytherapy in facial rejuvenation. This study included 60 patients with facial wrinkles. Patients were divided into three groups. Group 1 was treated with IPL, group 2 was treated with radiofrequency while group 3 was treated with carboxytherapy. All patients received four sessions with 3-4 week interval and followed up after 3 months after the end of treatment. Patients were assessed by digital photographing and skin biopsies before and after treatment. There was a significant difference in the percentage of improvement and patients' satisfaction with more significance in group 1, followed by group 3 then group 2. IPL was the more effective, followed by carboxytherapy then RF at the end in facial rejuvenation. These results were confirmed by immunohistochemical expression of MMP1.

Marine-Inspired Bis-indoles Possessing Antiproliferative Activity against Breast Cancer; Design, Synthesis, and Biological Evaluation.

Diverse indoles and bis-indoles extracted from marine sources have been identified as promising anticancer leads. Herein, we designed and synthesized novel bis-indole series 7a-f and 9a-h as Topsentin and Nortopsentin analogs. Our design is based on replacing the heterocyclic spacer in the natural leads by a more flexible hydrazide linker while sparing the two peripheral indole rings. All the synthesized bis-indoles were examined for their antiproliferative action against human breast cancer (MCF-7 and MDA-MB-231) cell lines. The most potent congeners 7e and 9a against MCF-7 cells (IC50 = 0.44 ± 0.01 and 1.28 ± 0.04 µM, respectively) induced apoptosis in MCF-7 cells (23.7-, and 16.8-fold increase in the total apoptosis percentage) as evident by the externalization of plasma membrane phosphatidylserine detected by Annexin V-FITC/PI assay. This evidence was supported by the Bax/Bcl-2 ratio augmentation (18.65- and 11.1-fold compared to control) with a concomitant increase in the level of caspase-3 (11.7- and 9.5-fold) and p53 (15.4- and 11.75-fold). Both compounds arrested the cell cycle mainly in the G2/M phase. Furthermore, 7e and 9a displayed good selectivity toward tumor cells (S.I. = 38.7 and 18.3), upon testing of their cytotoxicity toward non-tumorigenic breast MCF-10A cells. Finally, compounds 7a, 7b, 7d, 7e, and 9a were examined for their plausible CDK2 inhibitory action. The obtained results (% inhibition range: 16%-58%) unveiled incompetence of the target bis-indoles to inhibit CDK2 significantly. Collectively, these results suggested that herein reported bis-indoles are good lead compounds for further optimization and development as potential efficient anti-breast cancer drugs.

Synthesis, antitumor testing and molecular modeling study of some new 6-substituted amido, azo or thioureido-quinazolin-4(3H)-ones.

A new series of 6-substituted amido, azo or thioureido-quinazolin-4(3H)-one was synthesized and tested for their in-vitro antitumor activity. Compounds 21, 53 and 60 showed broad spectrum antitumor activity with average IC50 values of 6.7, 7.6 and 9.1 µM, respectively compared with methotrexate (1, IC50 19.26 µM). As an attempt to reveal the mechanism of the antitumor potency, cell cycle analysis and DHFR inhibition were performed. Compounds 59 and 61 induced their cytotoxicity in Hela (IC50 10.6 µM) and HCT-116 (IC50 15.5 µM) cell lines, respectively through Pre-G1 apoptosis, inhibiting cell growth at G2-M phase. Compounds 29, 33, 59 and 61 showed DHFR inhibitory potency at IC50 0.2, 0.2, 0.3 and 0.3 µM, respectively. The active DHFR inhibitors showed high affinity binding toward the amino acid residues Thr56, Ser59 and Ser118. The active compounds obeyed Lipinski's rule of five and could be used as template model for further optimization.

Targeting microbial resistance: Synthesis, antibacterial evaluation, DNA binding and modeling study of new chalcone-based dithiocarbamate derivatives.

New dithiocarbamate chalcone-based derivatives were synthesized, their structures were elucidated using different spectroscopic techniques. They were subjected to antimicrobial screening against selected Gram negative bacteria focusing on microbial resistance. Bacterial resistance was targeted via phosphoethanolamine transferase enzyme. Most of the synthesized compounds showed equal or higher activity to colistin standard. Compound 24 proved to be the most active candidate with MIC of 8 µg/ml against both Ps12 and K4 and MBC of 32 µg/ml against Ps12 and 16 µg/ml against K4 Molecular docking study showed that 20, 22, 24 and 25 had good binding affinity with active site residues via Thr280. DNA macromolecule was further targeted. Compounds 28 and 34 were recorded to have better DNA binding than doxurubucin with IC50 of 27.48 and 30.97 µg/ml respectively, suggesting that it could have a role in their higher antibacterial effect. Their docking into DNA has shown a clear intercalation matching with antibacterial data. Pharmacokinetics parameters of active compounds showed that they have better absorption through GIT.

New benzimidazothiazole derivatives as anti-inflammatory, antitumor active agents: Synthesis, in-vitro and in-vivo screening and molecular modeling studies.

A new series of benzimidazothiazole derivatives has been synthesized. The structure of the products was confirmed by spectroscopic techniques such as IR, NMR and mass spectroscopy. The tested compounds were evaluated for their anti-inflammatory activity either in vitro through the COX enzyme inhibition assay, or in vivo through carrageenan paw edema technique. Results revealed that compound 25 and 29 represented the most active ones among the entire series with % inhibition 72.19, 72.07 for COX-1, and 87.46, 87.38 for COX-2, respectively. Interestingly, all synthesized compounds exhibited IC50 values less than both reference drugs celecoxib and naproxen, indicating their superior potency. For compound 25, it showed about 340 and 198 times more potent than celecoxib and naproxen respectively as COX-1 inhibitor (IC50 value 0.044 vs. 15.000 and 8.700 µM), and 10 and 115 times more potent than the same drugs as COX-2 inhibitor (IC50 value 4.52 vs. 40.00 and 520.00 nM). The antitumor activity of the products was also evaluated and the results obtained are consistent with those obtained by the anti-inflammatory screening where compounds 25 and 29 proved to be the most active ones among the other compounds with %GI ranging from 31.5 to 62.5% and they exhibited the lowest IC50 values as well. The ADMET analysis of the tested compounds was also performed in addition to the molecular modeling studies that included flexible alignment, surface and electrostatic maps in addition to the Lipinisk's rule of five.

Synthesis, biological evaluation and in silico studies with 4-benzylidene-2-phenyl-5(4H)-imidazolone-based benzenesulfonamides as novel selective carbonic anhydrase IX inhibitors endowed with anticancer activity.

In the presented work, we report the synthesis of a series of 4-benzylidene-2-phenyl-5(4H)-imidazolone-based benzenesulfonamides 7a-fvia the Erlenmeyer-Plöchl reaction. All the prepared imidazolones 7a-f were evaluated as inhibitors of human (h) carbonic anhydrases (CA, EC 4.2.1.1) cytosolic isoforms hCA I and II, as well as transmembrane tumor-associated isoforms hCA IX and XII. All the tested hCA isoforms were inhibited by the prepared imidazolones 7a-f in variable degrees with the following KIs ranges: 673.2-8169 nM for hCA I, 61.2-592.1 nM for hCA II, 23-155.4 nM for hCA XI, and 21.8-179.6 nM for hCA XII. In particular, imidazolones 7a, 7e, and 7f exhibited good selectivity towards the tumor-associated isoforms (CAs IX and XII) over the off-target cytosolic (CAs I and II) with selectivity index (SI) in the range of 6.2-19.4 and 3.3-8, respectively. Moreover, imidazolones 7a-f were screened for their anticancer activity in one dose (10-5 M) assay against a panel of 60 cancer cell lines according to US-NCI protocol. Furthermore, 7a, 7e and 7f were evaluated for their anti-proliferative activity against colorectal cancer HCT-116 and breast cancer MCF-7 cell lines. Furthermore, 7e and 7f were screened for cell cycle disturbance and apoptosis induction in HCT-116 cells. Finally, a molecular docking study was carried out to rationalize the obtained results.

5-Thioxoimidazolidine-2-one derivatives: Synthesis, anti-inflammatory activity, analgesic activity, COX inhibition assay and molecular modelling study.

A series of 5-imino-4-thioxo-2-imidazolidinone derivatives with different substituents at N1 and N3 was synthesized with high yield and excellent purity by the reaction of different N-arylcyanothioformamide derivatives with isocyanate derivatives. Treatment 5-imino-4-thioxo-2-imidazolidinone derivatives with acidic medium afforded 4-thioxoimidazolidin-2,5-dione derivatives. The structures of the obtained products were established based on spectroscopic IR, 1H NMR, 13C NMR, 1H, 1H-COSY, HSQC and elemental analyses. The anti-inflammatory activity of the synthesized compounds through the carrageenan-paw edema model as well as in vitro COX-1 and COX-2 inhibition assay were evaluated where most of the synthesized compounds showed significant anti-inflammatory activity. Mostly, all of our synthesized compounds have greater activity more than celecoxib toward both cyclooxygenase enzymes. All of the tested compounds (except one compound) exhibited IC50 valves for COX-2 ranged from 0.001 × 10-3 to 0.827 × 10-3 µM while the reference drug has IC50 40.0 × 10-3 µM. Furthermore, the analgesic activity of such compounds was also determined. Molecular modeling study was also conducted to rationalize the potential as anti-inflammatory agents of our synthesized compounds by predicting their binding modes, binding affinities and optimal orientation at the active site of the COX enzymes.

Towards breast cancer targeting: Synthesis of tetrahydroindolocarbazoles, antibreast cancer evaluation, uPA inhibition, molecular genetic and molecular modelling studies.

A series of some new tetrahydroindolocarbazole derivatives has been synthesized. The structure of the synthesized compounds has been confirmed by different spectroscopic techniques such as IR, NMR, elemental analysis and mass spectrometry. The target compounds were evaluated for their antitumor activity against breast cancer cell line MCF-7, their GI% and their LC50 have been determined. Six of the synthesized compounds exhibited GI% values against MCF-7 cell lines exceeding 70% ranging from 71.9 to 85.0% in addition that compound 11 expressed GI% values of 99.9% and considered the most active derivatives among the synthesized ones. Compound 11 showed a remarkable decrease of u PA level to 3.5 ng/ml compared to DOX. Compound 5, 11 and 15 showed significant decrease in expression of MTAP and CDKN2A, in addition to a remarkable decrease in DNA damage comet assay method. Molecular modeling studies were performed to interpretate the behavior of active ligands as uPA inhibitors.