Anti-breast Cancer Agents Research Articles

Recent developments of hydroxamic acid hybrids as potential anti-breast cancer agents.

Histone deacetylase inhibitors not only possess favorable effects on modulating tumor microenvironment and host immune cells but also can reactivate the genes silenced due to deacetylation and chromatin condensation. Hydroxamic acid hybrids as promising histone deacetylase inhibitors have the potential to address drug resistance and reduce severe side effects associated with a single drug molecule due to their capacity to simultaneously modulate multiple targets in cancer cells. Accordingly, rational design of hydroxamic acid hybrids may provide valuable therapeutic interventions for the treatment of breast cancer. This review aimed to provide insights into the in vitro and in vivo anti-breast cancer therapeutic potential of hydroxamic acid hybrids, together with their mechanisms of action and structure-activity relationships, covering articles published from 2020 to the present.

Current scenario of chalcone hybrids with antibreast cancer therapeutic applications.

Breast cancer, an epithelial malignant tumor that occurs in the terminal ducts of the breast, is the most common female malignancy. Currently, approximately 70%-80% of breast cancer with early-stage, nonmetastatic disorder is curable, but the emergency of drug resistance often leads to treatment failure. Moreover, advanced breast cancer with distant organ metastases is incurable with the available therapeutics, creating an urgent demand to explore novel antibreast cancer agents. Chalcones, the precursors for flavonoids and isoflavonoids, exhibit promising activity against various breast cancer hallmarks, inclusive of proliferation, angiogenesis, invasion, metastasis, inflammation, stemness, and regulation of cancer epigenetics, representing useful scaffolds for the discovery of novel antibreast cancer chemotherapeutic candidates. In particular, chalcone hybrids could act on two or more different biological targets simultaneously with more efficacy, lower toxicity, and less susceptibility to resistance. Accordingly, there is a huge scope for application of chalcone hybrids to tackle the present difficulties in breast cancer therapy. This review outlines the chalcone hybrids with antibreast cancer potential developed from 2018. The structure-activity relationshipsas well as mechanisms of action are also discussed to shed light on the development of more effective and multitargeted chalcone candidates.

THE POTENTIAL EFFECT OF APORPHINE ALKALOIDS FROM NELUMBO NUCIFERA GAERTN. AS ANTI-BREAST CANCER BASED ON NETWORK PHARMACOLOGY AND MOLECULAR DOCKING

Objective: To demonstrate the efficacy and benefits of aporphine alkaloids from Nelumbo nucifera Gaertn. as anti-breast cancer agents. Methods: In this study, a combination of network pharmacology and molecular docking was used to investigate the pharmacological actions and underlying mechanisms of action of nuciferine, nor-nuciferine, and roemerine against breast cancer. Results: Fifty-five potential targets of compounds against breast cancer were identified. The Epidermal Growth Factor Receptor (EGFR), Mitogen-Activated Protein Kinase 8 (MAPK8), Janus Kinase 2 (JAK2), Inhibitor of Nuclear Factor Kappa B Kinase Subunit Beta (IKBKB), and Protein Kinase C Epsilon (PRKCE) were identified as the top five targets of compounds against breast cancer. Molecular docking demonstrated that these compounds could bind spontaneously to the screened top 4 targeted proteins. Conclusion: The present study demonstrates that these compounds have pharmacological effects against breast cancer via a multi-target and multi-pathway manner.

Spectroscopic, computational, cytotoxicity, and docking studies of 6-bromobenzimidazole as anti-breast cancer agent.

6-Bromobenzimidazole (6BBZ) has been calculated in this study utilizing the 6-311++G(d,p) basis set and the Becke-3-Lee-Yang-Parr density functional approaches. The basic frequencies and geometric optimization are known. FTIR, FT-Raman, and UV-Vis spectra of the substance are compared between its computed and observed values. The energy gap between highest occupied molecular orbital-lowest unoccupied molecular orbital and molecule electrostatic potentials has been represented by charge density distributions that may be associated with the biological response. Time-dependent density functional theory calculations in the gas phase and dimethyl sulfoxide were carried out to ascertain the electronic properties and energy gap values using the same basis set. Molecular orbital contributions are investigated using the overlap population, partial, and total densities of states. Natural bond analysis was found to have strong electron delocalization by means of π(C4-C9) → π*(C5-C6), LP (N1) → π*(C7-C8), and LP(Br12) → π*(C5-C6) interactions. The Fukui function and Mulliken analysis have been explored on the atomic charges of the molecule. The nuclear magnetic resonance chemical shifts for 1 H and 13 C have been computed using the gauge-independent atomic orbital technique. With the highest binding affinity (-6.2 kcal mol-1 ) against estrogen sulfotransferase receptor (PDB ID: 1AQU) and low IC50 value of 17.23 μg/mL, 6BBZ demonstrated potent action against the MCF-7 breast cancer cell line. Studies on the antibacterial activity and ADMET prediction of the molecule have also been carried out.

In silico study for discovering novel thiazole derivatives as anti-breast cancer agents (MCF-7)

The work validated the pharmacokinetic characteristics and docking approach, and discovered novel thiazole compounds with MCF-7 breast anti-cancer efficacy using quantitative structure-activity relationships (QSAR) models. Using an experimental dataset of 53 thiazole derivatives with IC50 values, QSAR models were developed using multivariate linear regression (QSARMLR) and artificial neural networks (QSARANN). Eight descriptions, with statistical values of R2train = 0.875 and Q2LOO = 0.834, comprised the successfully developed QSARMLR model. Based on the descriptors of the QSARMLR model, which has statistical values of R2 = 0.918, Q2test = 0.934, and Q2CV = 0.916, the QSARANN neural network model with the architectural network of I(8)-HL(9)-O(1) has also been constructed. Using the AD and outliers analysis, the models were utilized to forecast 120 new design derivatives based on the thiazole framework, and the IC50 values of 10 new thiazole derivatives were determined. Additionally, the derivatives were assessed for resistance to estrogen-positive breast cancer by docking them onto the Polo-like kinases (Plk1) receptor and screening them for pharmacokinetic features in accordance with Lipinski and Ghose guidelines. Consequently, it was discovered that the thiazole TAZ5 had promising derivative activity against the primary MCF-7 breast cancer cell line.

Design, synthesis, in vitro and in silico evaluation of indole-based tetrazole derivatives as putative anti-breast cancer agents.

A series of new indole-tetrazole derivatives were designed and synthesized to develop potential anti-breast cancer agents. The compounds exhibited in vitro anti-proliferative activity against ER-α positive T-47D (IC50 = 3.82-24.43 μM), MCF-7 (IC50 = 3.08-22.65 μM), and ER-α negative MDA-MB-231 (IC50 = 7.69-19.4 μM) human breast cancer cell lines. Compounds 5d and 5f displayed significant anti-proliferative activity compared to bazedoxifene (IC50 = 14.23 ± 0.68 μM), with IC50 values of 10.00 ± 0.59 and 3.83 ± 0.74 μM, respectively, against the ER-α dominant T-47D cell line. Also, both compounds showed non-significant cytotoxicity against normal cells HEK-293. Further, the ER-α binding affinity of 5d and 5f was assessed through a fluorescence polarization-based competitive binding assay, where 5d and 5f have shown significant binding with IC50 = 5.826 and 110.6 nM, respectively, as compared to the standard drug bazedoxifene (IC50 = 339.2 nM). Western blot analysis confirmed that compound 5d reduced ER-α protein expression in T-47D cells, hindering its transactivation and signalling pathways. Additionally, a molecular docking study suggests that compounds 5d and 5f bind in such a fashion that induces conformational changes in the protein, culminating in their antagonistic effect. Pharmacokinetic profiles showed that the compounds possessed drug-like properties. Furthermore, molecular dynamics simulation studies establish the dynamic stability and conformational behaviour of the ER-α protein and ligand complex of both compounds. Additionally, 5d and 5f ensure biological feasibility as per their DFT analysis through HOMO-LUMO energy gap analysis. In conclusion, compounds 5d and 5f, exhibiting significant ER-α antagonistic activity, can act as potential lead compounds for anti-breast cancer therapies.

Design, 3D-QSAR, molecular docking, ADMET, molecular dynamics and MM-PBSA simulations for new anti-breast cancer agents

Breast cancer is the most frequent form of malignant tumor in women, and represents a major public health problem due to its high mortality rate. Although a multitude of therapeutic options exist for control of this disease, the emergence of resistance to current pharmaceutical treatments underscores the urgency of developing new anti- breast cancer drugs, with a focus on reducing the adverse effects associated with current therapeutic agents. The present study concerns a new series of (23) compounds based on 1,4-quinone and quinoline derivatives to design candidate drugs against breast cancer. For this purpose, integrated computational techniques were applied, including 3D-QSAR, molecular docking and molecular dynamics simulations (MD). CoMFA and CoMSIA were used to build a robust and highly reliable 3D-QSAR models. To validate the model's predictive capabilities, an external validation was carried out. The results of the best model (CoMSIA/SEA) revealed that electrostatic, steric and hydrogen bond acceptor fields had a significant effect on the anti-breast cancer activity of molecules studied. In addition, evaluation of ADMET properties determined whether these newly designed ligands were likely to be selected as drug-candidates. To confirm the binding stability of the selected ligands to aromatase (3S7S) and validate the molecular docking results, molecular dynamics simulations lasting 100 nanoseconds were performed by calculating RMSD, RMSF, RoG, H-bond, SASA and MM-PBSA parameters. As a result, only one designed compound (ligand 5) emerged as the most promising drug candidate for experimental in vitro and in vivo testing, due to its potential inhibition of breast cancer.

Melinjo Seeds (Gnetum gnemon L.) Antioxidant Activity and Cytotoxic Effects on MCF-7 Breast Cancer Cells: A Study Based on Tracing of Resveratrol Compound.

Breast cancer is one of the deadliest cancers worldwide. One of the polyphenols, namely, resveratrol, has been proven to have anticancer activity. Melinjo seeds which contain resveratrol need to be tested for their potential as an anti-breast cancer agent. This study aims to determine the antioxidant activity and cytotoxic effect of melinjo seeds based on solvent variations and resveratrol tracing. Extraction of melinjo seeds was performed using the soxhletation method. Antioxidant test was performed using the 2,2-diphenyl-1-picrylhydrazil method. The in vitro cytotoxic test was carried out using the microtetrazolium method. Cytotoxic test was carried out on MCF-7 breast cancer cells using a concentration range of melinjo seeds between 31,25 and 1000 μg/mL. Antioxidant and anticancer potentials are expressed in inhibitory concentration (IC)50 values. Resveratrol was traced using preparative high-performance liquid chromatography (Prep-HPLC). Melinjo seed ethanol extract provided the largest total phenolics (126,154 ± 0,865 mg GAE/g sample) and total flavonoids (44,576 ± 0,611 mg QE/g sample) among all solvent fractions. The antioxidant activity of melinjo seeds from ethanol extract, n-hexane fraction, ethyl acetate fraction, and ethanol fraction was 263,307 ppm, 317,595 ppm, 160,878 ppm, and 181,159 ppm, respectively. The ethyl acetate fraction of melinjo seeds showed the strongest cytotoxic effect (94.6 μg/mL) among all extracts and solvent fractions. Prep-HPLC showed that the ethanol extract of melinjo seeds contained resveratrol, while the ethanol and ethyl acetate fractions of melinjo seeds were thought to contain resveratrol derivatives. The antioxidant activity of melinjo seeds showed a cytotoxic effect on MCF-7 cells, which varied based on solvent polarity and total phenolic and total flavonoid. The ethyl acetate fraction which is thought to contain resveratrol derivatives provides the most potent antioxidant activity and cytotoxic effect. These results indicate that melinjo seeds containing resveratrol and its derivatives have the potential for anticancer of the breast. Further studies are still needed in determining the structure of resveratrol compounds and their derivatives to ensure their biological activity and mechanism of action.

Study of Gnetum gnemon metabolites as potential anti-breast and prostate cancer by metabolomic and molecular docking

Breast and prostate cancers are significant health concerns worldwide, demanding novel and effective therapeutic approaches. This study explores the potential of Gnetum gnemon seed metabolites as anticancers agent through metabolomic profiling and molecular docking analysis. Six metabolites from G. gnemon seed were identified, which met Lipinski’s rule of five criteria, suggesting their drug-like properties. A panel of 10 molecular target proteins, including PTGS1, PTGS2, ESR1, SIRT1, SIRT3, SIRT5, AKT1, JAK2, BRAF, and NOS3, relevant to breast and prostate cancer pathways, were selected for molecular docking simulations. The binding interactions and free binding energy assessments identified gnetol and gnetin C as the most promising metabolites, showing strong interactions with multiple target proteins. Gnetol exhibited potential in targeting ESR1 and SIRT5, suggesting a mechanism for breast cancer inhibition. On the other hand, gnetin C emerged as a potent allosteric inhibitor of AKT1, potentially impacting breast and prostate cancer pathways. These findings highlight G. gnemon metabolites, particularly gnetol and gnetin C, as potential candidates for further preclinical and clinical studies as anti-breast and prostate cancer agents.

Integrated Network Ethnopharmacology, Molecular Docking, and ADMET Analysis Strategy for Exploring the Anti-Breast Cancer Activity of Ayurvedic Botanicals Targeting the Progesterone Receptor

Abstract Background: In women, breast cancer is currently among the most common cancers and the second major cause of cancer-related mortality. One therapeutic target for breast cancer is the progesterone receptor (PR), which can be inhibited by specific PR modulators. Methods: Current anti-cancer medications have notorious adverse effects. Consequently, an urgent need exists to identify less hazardous, more effective medicines with few to no adverse effects. One strategy uses ancient herbal remedies to create medications derived from nature. Herein, we used data from the Dr. Duke, IMPPAT, PubChem, Binding DB, UniProt, and DisGeNET databases to construct a network in Cytoscape 3.10.0. Through a polypharmacology approach, bioactives with similarity indices greater than 0.6 were screened and docked with the PR. The top ten ligands with good docking scores were further subjected to interaction analysis in AutoDock v.4.2 software. We additionally analyzed the ADMET properties of the phytochemicals. Results: Procurcumenol and alpha-turmerone exhibited superior interactions with PR, with binding affinities of −7.85 kcal/mol. All compounds met Lipinski’s rule of five and were effective ligands for the PR according to ADMET data analysis. Our findings suggest that procurcumenol and alpha-turmerone may serve as potential anti-breast cancer agents; specifically targeting the PR in breast cancer cells. Conclusion: Understanding of anti-breast cancer activity can be facilitated through experimental validation of network analysis and molecular docking findings.

Spectroscopic, Computational, Docking and Cytotoxicity Studies on 2-(2-Chlorophenyl)benzimidazole as a Potent Anti-breast Cancer Agent

Spectroscopic, Computational, Docking and Cytotoxicity Studies on 2-(2-Chlorophenyl)benzimidazole as a Potent Anti-breast Cancer Agent

Potential of Malang Robusta Coffee Beans as Anti-breast Cancer In-Vitro

Robusta coffee from Malang Regency, East Java is one of the superior products of the largest coffee-producing region in Indonesia. The coffee has high antioxidants. The component that acts as an antioxidant is the tannin content, and these tannins are also anti-cancer. Using the UV-Vis spectrophotometry method the tannin content in Malang Robusta coffee beans is known and then to measure its ability as an anticancer in-vitro against breast cancer cells using MCF-7. The results showed that the tannin contained in Malang Robusta coffee bean extract was 2.81 % and inhibited MCF-7 at 400 µg/mL, it has potential as an anticancer with an inhibition value of 68.88 %. Therefore, the use of Robusta coffee from Malang at this concentration can be used as an anti-breast cancer agent.

The Active Compound Content of Jamblang (Syzygium cumini) as an Anti-Breast Cancer

Jamblang is rich in bioactive compounds such as anthocyanins, phenolics, and flavonoids. Anthocyanins, which give jamblang fruit its dark color, have been known for their antioxidant properties that can fight oxidative stress, which is linked to the development of cancer. Phenolics, with their anti-inflammatory and antioxidant properties, provide additional protection to body cells. Flavonoids, with a wide range of biological activities, including anti-cancer properties, could potentially be promising agents in cancer prevention and treatment efforts. The literature search process was carried out on various databases (PubMed, Web of Sciences, EMBASE, Cochrane Libraries, and Google Scholar) regarding the potential of the active compound Jamblang (Syzygium cumini) as anti-breast cancer. This study follows the preferred reporting items for systematic reviews and meta-analysis (PRISMA) recommendations. The jamblang plant has potential as an anti-breast cancer agent. Jamblang plants are rich in active compounds that have anticancer activity, namely anthocyanins, flavonoids, phenolic compounds and carotenoids. These compounds can inhibit cancer cell growth, trigger apoptosis, and inhibit metastasis.

Synthesis, characterization and <i>In-silico</i> study of anti-cancer potential of Cu(II) and Ni(II) complexes of (E)-2- benzylidenehydrazinecarboxamide

In this study, (E)-2-benzylidenehydrazinecarboxamide coordination compounds and mixed ligand metal complexes with oxalic acid or 1,2-diaminocyclohexane were synthesized. Their potential cytotoxic effects and interactions with B-DNA evaluated. This was with a view to demonstrate their potential as anticancer agents for breast cancer. (E)-2-Benzylidenehydrazinecarboxamide (benzaldehyde semicarbazone) coordination compounds of Cu(II) and Ni(II) and mixed ligand metal complexes with oxalic acid and 1,2- diaminocyclohexane were synthesized. The resultant complexes were characterized by physicochemical techniques including melting point measurement, percent metal analysis, solubility, and magnetic susceptibility measurements. Electronic and Fourier transform infrared (FTIR) spectroscopy, were performed to further lucidate the structures of the complexes. The synthesized compounds were examined for their cytotoxic effects and DNA interactions with B-DNA. The results obtained showed that all the ligands used were bidentate ligands. They bound to the metal ions through oxygen and nitrogen atoms. All synthesized compounds showed good cytotoxic activity against brine shrimp nauplii except for the (E)-2-benzylidenehydrazinecarboxamide copper(II) complex. All of the metal complexes, with the exception of the (E)-2- enzylidenehydrazinecarboxamide coordination copper complex, bound to DNA with moderate binding energies. They favoured conventional hydrogen bonding and hydrophobic interaction mostly. The copper complex with 1,2-diaminocyclohexane had the most interaction and a good binding effect to the DNA and better than oxaliplatin, the standard used. This therefore indicated the potential of these compounds as probable chemotherapeutic agents against breast cancer cells.

Design, synthesis, and evaluation of 4-(3-(3,5-dimethylisoxazol-4-yl)benzyl)phthalazin-1(2H)-one derivatives: potent BRD4 inhibitors with anti-breast cancer activity

BRD4 inhibitors have demonstrated promising potential in cancer therapy. However, their therapeutic efficacy in breast cancer varies depending on the breast cancer subtype, particularly in the treatment of TNBC. In this study, we designed and synthesized 94 derivatives of 4-(3-(3,5-dimethylisoxazol-4-yl)benzyl)phthalazin-1(2H)-one to evaluate their inhibitory activities against BRD4. Notably, compound DDT26 exhibited the most potent inhibitory effect on BRD4, with an IC50 value of 0.237 ± 0.093 μM. DDT26 demonstrated significant anti-proliferative activity against both TNBC cell lines and MCF-7 cells. Intriguingly, the phthalazinone moiety of DDT26 mimicked the PAPR1 substrate, resulting in DDT26 displaying a moderate inhibitory effect on PARP1 with an IC50 value of 4.289 ± 1.807 μM. Further, DDT26 was shown to modulate the expression of c-MYC and γ-H2AX, induce DNA damage, inhibit cell migration and colony formation, and arrest the cell cycle at the G1 phase in MCF-7 cells. Our findings present potential lead compounds for the development of potent anti-breast cancer agents targeting BRD4.

Benzothiazole-Phthalimide Hybrids as Anti-Breast Cancer and Antimicrobial Agents.

The benzothiazole nucleus is a major heterocyclic scaffold whose therapeutic potential has been thoroughly explored due to its structural simplicity and ease of synthesis. In fact, several benzothiazole derivatives have been synthesized over time, demonstrating numerous pharmacological properties such as anticancer, antimicrobial, anti-inflammatory, and antioxidant activities. Herein, we propose a new series of benzothiazole-phthalimide hybrids obtained by linking the phthalimide moiety to differently substituted benzothiazole nuclei through the N atom. These compounds have been screened for their anticancer properties against two human breast cancer cell lines. Furthermore, we delved into the mechanism of action of the most active hybrid, compound 3h, by assessing its capability to damage the nuclear DNA, trigger the apoptotic process in the high metastatic MDA-MB-231 cells, and prevent cellular migration. Moreover, in view of the documented antimicrobial activities of the two scaffolds involved, we explored the antibacterial and antifungal effects of the studied compounds by means of the broth microdilution method. Among the studied compounds, 3h showed the highest antimicrobial activity, both against gram-positive and gram-negative bacterial strains belonging to the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) and against fungal strains of the Candida species with MICs values ranging from 16 to 32 µg/mL.

Cyclometalated iridium(III) complexes as anti-breast cancer and anti-metastasis agents via STAT3 inhibition

Breast cancer is the most commonly diagnosed cancer and second‑leading cause of cancer deaths in women. Signal transducer and activator of transcription 3 (STAT3) plays a critical role in promoting breast cancer cell proliferation, invasion, angiogenesis, and metastasis, and the high expression of STAT3 is related to the occurrence and poor chemotherapy sensitivity of breast cancer. Iridium(III) complexes Ir-PTS-1– 4 containing a pterostilbene-derived ligand were synthesized to inhibit the STAT3 pathway in breast cancer. Ir-PTS-4 inhibited the proliferation of breast cancer cells by suppressing the expression of phosphorylated STAT3 and STAT3-related cyclin D1, arresting cell cycle in the S-phase, inducing DNA damage and reactive oxygen species (ROS) generation, eventually leading to autophagic cell death. The cell metastasis and invasion were also inhibited after Ir-PTS-4 treatment. Besides, Ir-PTS-4 exhibited excellent anti-proliferation activity in 3D multicellular tumor spheroids, showing potential for the treatment of solid tumors. This work presents the rational design of metal-based anticancer agents to block the STAT3 pathway for simultaneously inhibiting breast cancer proliferation and metastasis.

Potential of Natural products for Chemoprevention of Breast Cancer

Background: Breast cancer is the most frequent female cancer and one of the leading causes of cancer death in women. There are many chemotherapy agents available for the treatment of breast cancer. Still, the current therapeutic options have not fulfilled the desired outcomes, especially for drug-resistant breast cancer therapy. Thus, there is an urgent need to develop novel anti-breast cancer agents. Objective: This overview targets to portray the new advancement of herbal and artificial derivatives with anti-breast cancer potential, protecting the articles allotted from the ultimate year. Method: We found significant articles of interest in the field of breast cancer and proposed a review based on relevant information. Description of the studies included in the review. Result: Various key components are found in vegetables, fruits, seeds, nuts, coffee, tea, and wine. Therefore, dietary exposure is significant. Natural products having low-cost toxicity, their availability in foods, and their existence in a variety of herbal treatments, caution should be exercised in further assessment of their properties and applications. Conclusion: We tried to analyze the anti-breast cancer potency of quite a few extracts from different plant sources and to compare their antiproliferative efficiency of crude extracts with the action of their purified ingredients while an additional study is required.

2-Amino Thiazole Derivatives as Prospective Aurora Kinase Inhibitors against Breast Cancer: QSAR, ADMET Prediction, Molecular Docking, and Molecular Dynamic Simulation Studies.

The aurora kinase is a key enzyme that is implicated in tumor growth. Research revealed that small molecules that target aurora kinase have beneficial effects as anticancer agents. In the present study, in order to identify potential antibreast cancer agents with aurora kinase inhibitory activity, we employed QSARINS software to perform the quantitative structure-activity relationship (QSAR). The statistical values resulted from the study include R2 = 0.8902, CCCtr = 0.7580, Q2 LOO = 0.7875, Q2LMO = 0.7624, CCCcv = 0.7535, R2ext = 0.8735, and CCCext = 0.8783. Among the four generated models, the two best models encompass five important variables, including PSA, EstateVSA5, MoRSEP3, MATSp5, and RDFC24. The parameters including the atomic volume, atomic charges, and Sanderson's electronegativity played an important role in designing newer lead compounds. Based on the above data, we have designed six series of compounds including 1a-e, 2a-e, 3a-e, 4a-e, 5a-e, and 6a-e. All these compounds were subjected to molecular docking studies by using AutoDock v4.2.6 against the aurora kinase protein (1MQ4). Among the above 30 compounds, the 2-amino thiazole derivatives 1a, 2a, 3e, 4d, 5d, and 6d have excellent binding interactions with the active site of 1MQ4. Compound 1a had the highest docking score (-9.67) and hence was additionally subjected to molecular dynamic simulation investigations for 100 ns. The stable binding of compound 1a with 1MQ4 was verified by RMSD, RMSF, RoG, H-bond, molecular mechanics-generalized Born surface area (MM-GBSA), free binding energy calculations, and solvent-accessible surface area (SASA) analyses. Furthermore, newly designed compound 1a exhibited excellent ADMET properties. Based on the above findings, we propose that the designed compound 1a may be utilized as the best theoretical lead for future experimental research of selective inhibition of aurora kinase, therefore assisting in the creation of new antibreast cancer drugs.

Bioevaluation of spiro N-propargylic β-enaminones as anti-breast cancer agents: Cell cycle and molecular docking studies.

The study aimed to investigate the in vitro inhibitory activities of spiro N-propargylic β-enaminones (SPEs) (1-31) against breast cancer cells (BCa). Cytotoxic activity was investigated via MTT assay. DNA fragmentation was evaluated via ELISA assay. Cell cycle distributions were investigated by flow cytometry. Expression levels of Bcl-2, Bax, p21 and Cyclin D1 were measured by qRT-PCR and western blot analysis. Autodock/vina software was used to understand the interaction between the SPEs and the ERα, PR, EGFR, and Her2. ADMETlab 2.0 tool was used to determine the drug-likeness properties. Notably, SPEs 1, 22, and 28 displayed selective cytotoxicity and apoptosis against BCa cells. They arrested the cell cycle at the S phase, inducing p21 and Cyclin D1. SPE1, SPE22, and SPE28 exhibited strong affinity for BCa receptors and drug-like properties. Pending in vivo validation with safety assurance for human health, these compounds hold potential as chemotherapy candidates.