Anti-breast Cancer Agents Research Articles

Vanillin-Based Indolin-2-one Derivative Bearing a Pyridyl Moiety as a Promising Anti-Breast Cancer Agent via Anti-Estrogenic Activity.

The structure-based design introduced indoles as an essential motif in designing new selective estrogen receptor modulators employed for treating breast cancer. Therefore, here, a series of synthesized vanillin-substituted indolin-2-ones were screened against the NCI-60 cancer cell panel followed by in vivo, in vitro, and in silico studies. Physicochemical parameters were evaluated with HPLC and SwissADME tools. The compounds demonstrated promising anti-cancer activity for the MCF-7 breast cancer cell line (GI = 6-63%). The compound with the highest activity (6j) was selective for the MCF-7 breast cancer cell line (IC50 = 17.01 μM) with no effect on the MCF-12A normal breast cell line supported by real-time cell analysis. A morphological examination of the used cell lines confirmed a cytostatic effect of compound 6j. It inhibited both in vivo and in vitro estrogenic activity, triggering a 38% reduction in uterine weight induced by estrogen in an immature rat model and hindering 62% of ER-α receptors in in vitro settings. In silico molecular docking and molecular dynamics simulation studies supported the stability of the ER-α and compound 6j protein-ligand complex. Herein, we report that indolin-2-one derivative 6j is a promising lead compound for further pharmaceutical formulations as a potential anti-breast cancer drug.

Design, synthesis, and in vitro cytotoxicity evaluation of novel dihydroartemisinin-isatin hybrids tethered via different length of esters as potential anti-breast cancer agents

In the present work, we reported the design, synthesis, and in vitro cytotoxicity evaluation of novel dihydroartemisinin-isatin hybrids tethered via different length of esters against MCF-7, MDA-MB-231, MCF-7/ADR and MDA-MB-231/ADR breast cancer cell lines. The preliminary results showed that the majority of the hybrids exhibited good anti-breast cancer cell activity. In particular, hybrids 7 g and 7n not only were more potent than ART, DHA and ADR against the four tested breast cancer cell lines, but also were non-toxic towards normal MCF-10A breast cells. The selectivity index values of hybrids 7 g and 7n were > 12.83 and > 25.97 respectively, revealing their excellent safety and selectivity profiles. The drug-resistant index values of hybrids 7 g and 7n were in a range of 0.33 to 1.12, implying that these hybrids had the potential to overcome drug resistance. Accordingly, hybrids 7 g and 7n could be considered as potential lead molecules for the development of novel anti-breast cancer agents with minimal untoward events to normal human cells. The structure-activity relationships indicated that the length of ester likner between DHA and isatin as well as substituents at C-3 and C-5 positions of isatin moiety had great impact on the activity.

Design, synthesis, molecular docking and biological evaluation of 1,2,4-triazole derivatives possessing a hydrazone moiety as anti-breast cancer agents

A set of 1,2,4-triazoles containing a hydrazone moiety was synthesized by oxidative cyclization utilizing molecular iodine under mild conditions. These compounds were evaluated as anticancer agents and their binding mechanism was investigated.

Green synthesis of gold nanoparticles as an effective opportunity for cancer treatment

Nanotechnology has proven to be a technology capable of generating anti-cancer nanoparticles in an environmentally friendly approach. Nanoparticles are usually created using a variety of processes that have a detrimental effect on the environment. Incorporating plant extracts with nanoparticles is an alternative, conservative method. In our research, gold nanoparticles were prepared by two aqueous extracts of Ziziphus spina-christi leaves and Cordia myxa L. leaves, and diagnosed using TEM, FE-SEM and AFM. The ability of gold nanoparticles as an anti-breast cancer agent was tested against MCF-7 cell line in synergistic with near-infrared radiation (NIR) at 808 nm. It was found that radiation enhances the properties of gold nanoparticles as a cancer treatment by converting the absorbed light into heat in a short time through a series of non-radiative processes.

Molecular docking and ADMET studies to predict the anti-breast cancer effect of aloin by targeting estrogen and progesterone receptors

The existing anti-cancer drugs are known for their adverse effects. Hence, it calls for an urgent need to explore the alternative therapies that are safer and efficient with no or minimal side effects. This approach points towards the utilization of traditional medicinal herbs to formulate naturally-derived drugs. So, aloin is a bioactive compound of Aloe Vera and known to exhibit an anticancerous effect on different cancer types. However, limited studies are indicating its possible interaction with estrogen receptors (ER) and progesterone receptors (PGR), that are the most targeted receptors in breast cancer therapeutics. Our study aims to predict the possible interactions of ER and PGR with aloin. We also analysed the drug likeliness properties of aloin for its anti-breast cancer activity. Hence, we performed molecular docking study of aloin against both these receptors using AutodockVina. Drug-like properties and bioactivity score for aloin was also predicted, using Molinspiration tool. The results suggest that aloin exhibit better interaction with ER than PGR with a binding affinity of −8.0 Kcal/mol. Molinspiration assay further suggested the aloin to carry drug-like property and behave as a good ligand for nuclear receptors. Our study indicates that aloin may behave as a potential anti-breast cancer agent by targeting the ER in breast cancer cells.

Therapeutic significance of molecular hybrids for breast cancer research and treatment.

Worldwide, breast cancer is still a leading cause of cancer death in women. Indeed, over the years, several anti-breast cancer drugs have been developed; however, the complex heterogeneous nature of breast cancer disease reduces the applicability of conventional targeted therapies with the upsurge in side effects and multi-drug resistance. Molecular hybrids generated by a combination of two or more active pharmacophores emerged as a promising approach in recent years for the design and synthesis of anti-breast cancer drugs. The hybrid anti-breast cancer molecules are well known for their several advantages compared to the parent moiety. These hybrid forms of anti-breast cancer molecules demonstrated remarkable effects in blocking different pathways contributing to the pathogenies of breast cancer and improved specificity. In addition, these hybrids are patient compliant with reduced side effects and multi-drug resistance. The literature revealed that molecular hybrids are applied to discover and develop novel hybrids for various complex diseases. This review article highlights the recent progress (∼2018-2022) in developing molecular hybrids, including linked, merged, and fused hybrids, as promising anti-breast cancer agents. Furthermore, their design principles, biological potential, and future perspective are discussed. The provided information will lead to the development of novel anti-breast cancer hybrids with excellent pharmacological profiles in the future.

Design, synthesis and evaluation of novel 3-(substitutedphenyl)-2-(4-(substitutedphenyl) thiazol-2-yl)-2hpyrazolo [3, 4-d] thiazol-5(6h)-one derivatives as anti-breast cancer agents

Mainstream cancer research has continued to place a significant emphasis on the development of new and effective therapeutic candidates to tackle rising treatment resistance and off-target toxicities. Here, a series of novel 3-(substitutedphenyl)-2-(4-(substitutedphenyl)thiazol-2-yl)-2Hpyrazolo[3,4-d]thiazol-5(6H)-one derivatives were synthesized and characterized. The ability of the synthesized compounds to reduce the survival of the human breast cancer cell line MDA-MB 231 was evaluated. When compared to the reference chemical, 5-fluorouracil, 3-(4-chlorophenyl)-2-(4- (4-chlorophenyl)thiazol-2-yl)-2H-pyrazolo[3,4d]thiazol-5(6H)-oneand 3-(4-nitrophenyl)-2-(4-(4-nitrophenyl)thiazol-2-yl)-2H-pyrazolo[3,4d]thiazol5(6H)-oneshowed the highest inhibitory activity (IC50:550 0.78 M and 504 0.89, respectively) on the viability of MDA-MB 231 cells. A molecular docking study has been carried out to discover more potent drugs.

Molecular docking, ADMET profiling of gallic acid and its derivatives (N-alkyl gallamide) as an anti-breast cancer agent

Background In 2020, breast cancer has become the most common cancer in the world and in Indonesia. Searching for anticancer drugs using computational methods is considered more effective and selective than other methods. Gallic acid and its derivatives (esters and amides) are compounds that have biological activities such as anticancer effects. The purpose of this study was to analyse the molecular modelling and ADMET (Adsorption, Distribution, Metabolism, Excretion and Toxicity) profile of gallic acid derivative compounds (N-alkyl gallamides) as anticancer agents. Methods Target proteins were selected by analysis of protein-protein and drug-protein interactions. Molecular modelling was done by molecular docking. Predictive analysis of the ADMET profile of gallic acid and its derivatives (N-alkyl gallamide) was conducted using Marvin Sketch, Swissadme, protox II, and pkCSM pharmacokinetics. The selected target proteins were JUN, AKT1, CASP3, and CASP7. Results Compounds N-octyl gallamide, N-ters-butyl gallamide, and N-isoamil gallamide were the three best gallic acid derivatives based on molecular modelling analysis of target proteins associated with breast cancer. The ADMET profile of the N-alkyl gallamide compound is predictable and shows a good profile as a candidate for anticancer drugs. Conclusion N-octyl gallamide, N-ters-butyl gallamide, and N-isoamil gallamide have potential as anti-breast cancer agents.

High-sensitivity troponin I as a predictor of left ventricular dysfunction in the use of cardiotoxic anticancer agents for breast cancer in patients with predominantly low and moderate risk of cardiotoxicity

Aim. To study the significance of monitoring high-sensitivity troponin I (hs-cTnI) for predicting anthracycline-induced left ventricular (LV) dysfunction in the treatment of breast cancer in patients with moderate and low risk of cardiotoxicity (CT).Material and methods. The study involved 49 patients with breast cancer aged 50±10 years who underwent neoadjuvant or adjuvant chemotherapy, which included doxorubicin at a course dose of 60 mg/m2 and an average cumulative dose of 251±60 mg/m2. The level of hs-cTnI was determined by an ultrasensitive method before the start of chemotherapy, after each course of anthracyclines and in 18 patients before the administration of anthracyclines. The level of hscTnI >0,017 ng/ml was considered elevated. Echocardiography was performed before the start of chemotherapy, after the end of anthracycline therapy, and every 3 months for 12 months thereafter. CT was defined as a decrease in LV ejection fraction (EF) by ≥10% to <53%.Results. CT risk before chemotherapy was considered low and moderate in 96% of patients. An increase in hs-сTnI was detected ≥1 times in 56,8% of patients: before chemotherapy — in 13,5%, after 1 and 2 courses of anthracycline therapy — in 13,9%, after 3, 4, 5 and 6 courses — in 44%, 62%, 71% and 66% of patients, respectively. The levels of hs-cTnI before and after administration of anthracyclines did not differ significantly. The development of LV dysfunction was observed in 16,3% of patients. There were following prognostic significance of an increase in hs-cTnI at any time of chemotherapy for a decrease in LV EF: sensitivity — 87,5%, specificity — 50%, the positive predictive value — 28%, the negative predictive value — 94,7%. The closest relationship was noted between CT and hs-cTnI value before the start of chemotherapy (β=0,45, p=0,005) and after the 3rd course of anthracycline therapy (β=0,56, p=0,002).Conclusion. An increase in hs-cTnI level before and during anthracycline thera py in patients with a low risk of cardiotoxicity has a prognostic value in relation to the development of left ventricular dysfunction. Hs-cTnI assessment should be performed before the start of therapy, and then starting from the 3rd course of anthracycline therapy in all patients, regardless of the risk of cardiotoxicity.

Folic acid-poly(N-isopropylacrylamide-maltodextrin) nanohydrogels as novel thermo-/pH-responsive polymer for resveratrol breast cancer targeted therapy

BackgroundThe long-term sequelae and serious side effects of conventional breast cancer chemotherapy due to ubiquitous biodistribution and systemic toxicity remain the main obstacle to success in clinic. Recent anticancer research rely on tailoring smart carriers to overcome these drawbacks. In this regard, numerous stimuli-responsive polymers have been assembled and successfully employed as smart carriers various chemotherpeutic agents due to their intrinsic tumor targeting properties. Among which, poly(N-isopropylacrylamide (PNIPAM) has gained increasing attention being amenable to various chemical modifications for tuning its intrinsic thermoresponsivity or endowing additional stimulus responsiveness. This work aims to develop PNIPAM-maltodextrin nanohydrogels (PNIPAM-MD NGs) decorated with folic acid (FA) as smart breast cancer-targeted stimuli-responsive delivery system to the natural polyphenol resveratrol (RSV) suffering from low bioavailaibity. ResultsPNIPAM-MD was synthesized by graft copolymerization, characterized and evaluated for its modulated stimuli-responsivity. The PNIPAM-based copolymer was coupled with FA, the breast cancer active targeting ligand. The FA-PNIPAM-MD NGs core was loaded RSV, then subjected to in vitro and in vivo evaluation. Results showed that the developed RSV-loaded FA-PNIPAM-MD (F3) NGs displayed dual thermo- and pH-responsivities, high drug-loading capacity (8.31 wt%,) and excellent physical and serum stability. The targeted formula F3 exhibited enhanced in vitro anti-breast cancer potency as evident by 7.4 folds reduction in the IC50 of free RSV and significant MCF-7 cellular uptake. In breast cancer-bearing mice, F3 suppressed the tumor growth, lowered VEGF-1 and Ki-67 expression levels, and induced apoptosis via upregulating caspase-3. ConclusionOverall, the PNIPAM-MD NGs as well as its FA-decorated breast cancer-targted NGs could serve as promising smart nanocarrier for efficient RSV brest cancer delivery. It could be safely deduced that the assembled FA-PNIPAM-MD F3 NGs enabled sequestering the therapeutic cargo (RSV) in normal tissue and released it in tumor site, thus guarding against its rapid metabolism and maximizing its accumulation in the cancer tissue as evidenced by the remarkable tumor growth suppression noticed in the targeted RSV/FA-PNIPAM-MD F3 NGs-treated mice compared to that in the free RSV-treated group. Hence, The fabricated nanohydrogels may be further employed for smart delivery of various anti-breast cancer agents.

S-phase arrest and apoptosis in human breast adenocarcinoma MCF-7 cells via mitochondrial dependent pathway induced by tricyclohexylphosphine gold (I) n-mercaptobenzoate complexes

We have previously reported the inhibition of thioredoxin reductase (TrxR) and invasion by tricyclohexylphosphine gold (I) n-mercaptobenzoate (n = 2, 3, 4) labeled as 1–3 towards MCF-7 cells, in vitro. Nevertheless, the mode of death and its apoptotic pathway has yet to be revealed. The main aim of this study is to investigate the anti-neoplastic activity of this phosphanegold (I) thiolates against breast adenocarcinoma cells, MCF-7. Herein, we explored the role of gold(I) series, 1–3 for their apoptosis-inducing ability against MCF-7 cells. They were scrutinized for their antiproliferative activities which exhibited their IC50 values of 8.14 μM ± 0.10, 7.26 μM ± 0.33, and 9.03 μM ± 0.69, respectively, and indicated better cytotoxicities than that of cisplatin (positive control). Further, the mechanisms of their actions were studied by analyzing the status of ROS generation (by DCFH-DA), cytochrome c release (by ELISA), and activation of caspases 3/7, 8, 9, and 10, annexin V staining and cell cycle analysis by flow cytometry, respectively. It was observed that the compounds, 1–3 can promote ROS generation, cytochrome c release, and activation of caspases 3/7, caspase 8, caspase 9, and caspase 10 on MCF-7 cells. In addition, the compounds are shown to induce MCF-7 cell arrest at S-phase. Gene analysis via PCR array further clarified their effects by modulating the related genes upon the compounds' treatment. Further investigation on other breast cancer cells as well as in vivo studies on these compounds will further increase their potential as anti-breast cancer agents.

Pharmacophore Modeling, 3D QSAR, Molecular Dynamics Studies and Virtual Screening on Pyrazolopyrimidines as anti-Breast Cancer Agents

Various targets, such as estrogen receptor (ER), mammalian target ofrapamycin(mTOR), epidermal growth factor receptor (EGFR), androgen receptor (AR) andpoly adenosine diphosphate-ribose polymerase (PARP), are focused on the treatment of breast cancer. In this study, in silico tools such as pharmacophore modeling, 3D QSAR study, molecular docking, binding free energy determination and molecular dynamics were executed on a series of pyrazolopyrimidines derivatives. The pharmacophore modeling of forty-one anticancer derivatives was generated, and atom-based 3D QSAR was applied. Molecular docking, dynamics, binding energy and high-throughput virtual screening (HTVS) were conducted by the software Schrodinger. The best five featured pharmacophore hypotheses AHRRR_1 with a maximum survival score of 5.533 was subjected to rigorous scoring function analysis and 3D QSAR studies. Docking studies and binding free energy were carried out on 41 inhibitors for their anti-breast cancer activity against human estrogen, progesterone receptor, EGFR kinase and mammalian target of rapamycin mTOR. Molecular dynamics simulation of the docked complex-34/4WKQ validated the stability of this complex. HTVS was performed to determine the virtual hits with the best-fitted model AHRRR_1. New EGFR kinase inhibitors were designed based on the active compound templates. Molecular docking was carried out on virtual hits, and newly designed compounds and dynamics studies revealed that the binding modes obtained after MD simulation were more or less similar to that acquired post docking mode. Promiscuity assessments demonstrated that designed compounds would be specific rather than a promiscuous one. Based on these findings, we have designed four novel compounds as anti-breast inhibitors, with potent binding affinity and desirable ADME properties.

Design, synthesis, spectral analysis and molecular docking studies of some cyclic imide as potential anti breast and cervical cancer agents

A number of cyclic imide derivatives were prepared in this study, using Diels- Alder reaction as a first step between maleic anhydride and anthracene. Use the reaction product as a reactant in the second step with different amines. The prepared cyclic imides were characterized by following the known spectroscopic methods to prove the proposed chemical composition of each of them using Mass, FT-IR, 1HNMR and 13CNMR. The biological activity of the prepared cyclic imides was tested theoretically using molecular docking to prove their efficacy as candidate inhibitors of breast and cervical cancer. The efficacy of prepared cyclic imides as inhibitors and antagonists of breast and cervical cancer, a practical candidate using the MTT assay to measure cellular metabolic activity as an indicator of cell viability, proliferation and cytotoxicity in MCF-7 and HeLa cell lines. Cytotoxic effects were in agreement with the molecular docking calculations, as the prepared cyclic imide derivatives showed good activity in inhibiting breast and cervical cancer cells. The results of MTT assay and molecular docking scores proved that the prepared (11R,15S)-13-(3-nitrophenyl)-9,10-dihydro-9,10-[3,4]epipyrrolo-anthracene-12,14-di one derivative a3 is considered as a potential candidate inhibitor for cervical cancer.

Clinical Significance of the Histone Deacetylase 2 (HDAC-2) Expression in Human Breast Cancer.

Background/Aim: There is a strong association between malignancy and histone deacetylases (HDACs). Histone deacetylase inhibitors (HDACIs) are now being tested as antitumor agents in various clinical trials. We aimed to assess the clinical importance of HDAC-2 in breast cancer (BC). Materials and Methods: A total of 118 BC specimens were examined immunohistochemically. A statistical analysis was conducted in order to examine the relation between HDAC-2 and the clinicopathological features and survival of the patients. Results: Higher HDAC-2 expression was related to lobular histological type of cancer, grade III, and stage III BC. In addition, the disease-free period and overall survival were curtailed and negatively related to the over-expression of HDAC-2. Other factors correlating with worse survival were histological types other than ductal or lobular, and the stage of the disease. Conclusions: This study showed a relationship between HDAC-2 and BC. Further studies are required in order to eventually potentiate the role of HDACIs as anticancer agents in BC.

Synthesis, docking studies, biological activity of carbon monoxide release molecules based on coumarin derivatives.

In the present work, we synthesized seven complexes. All complexes were identified by ESI-HRMS, 1H-NMR, 19F-NMR and 13C-NMR spectroscopies. The synthesized complexes were tested for their anticancer activities in vitro against three different human cell lines, including breast MDAMB231, cervical Hela, liver HepG2. IC50 values of complexes 1-7 were 34.98–667.35 µM. Complex 5 revealed higher sensitivity towards MDAMB231 cells with IC50 values 34.98 μM in comparison to 5-FU as positive control. Moreover, complex 5 caused a decrease of mitochondrial membrane potential and effectively induced ROS production against MDAMB231 cells. Western blot analysis showed that complex 5 could up-regulate the expression of Bax protein and down-regulate the expression of Bcl-2, activate Caspase-3, slightly down-regulate the expression of HO-1. The docking studies showed that complex 5 could be interacted with Bcl-2 protein through hydrophobic interactions, hydrogen bonds and salt bridges to enhance the binding affinity. All the analyzed coumarins obeyed the Lipinski’s rule of five for orally administered drugs. Based on the aforementioned results, it suggests that the complex induced apoptosis cell via mitochondria pathways. Collectively, complex 5 could be considered as a promising hit for new anti-breast cancer agents. Carbonyl cobalt CORMs, as potential anticancer therapeutic agents, provided a new idea for the development of metal anticancer drugs.

Synthesis, biological evaluation, and molecular modeling studies of new benzoxazole derivatives as PARP-2 inhibitors targeting breast cancer

Many benzoxazole-based and similar scaffolds were reported to have wide-range of anticancer activities. In this study, four series of benzoxazole derivatives were designed by combining benzoxazole scaffold with different amines via a reversed phenyl amide linker to produce the compounds of series A, B and C. A fourth new hybrid of benzoxazole with 1,2,3 triazole ring (series D) was also designed. The designed compounds were synthesized and screened for their anti-breast cancer activity against MDA-MB-231 and MCF-7 cell lines using MTT assay. The most potent cytotoxic compounds; 11–14, 21, 22, 25–27 were further evaluated for their in vitro PARP-2 enzyme inhibition. Compounds 12 and 27 proved to be the most active PARP-2 inhibitors with IC50 values of 0.07 and 0.057 µM, respectively. Compounds 12 and 27 caused cell cycle arrest in mutant MCF-7 cell line at G2/M and G1/S phase, respectively and they possessed significant apoptosis-promoting activity. Docking results of compounds 12 and 27 into PARP-2 pocket demonstrated binding interactions comparable to those of olaparib. Their predicted pharmacokinetic parameters and oral bioavailability appeared to be appropriate. Collectively, it could be concluded that compounds 12 and 27 are promising anti-breast cancer agents that act as PARP-2 inhibitors with potent apoptotic activity.

Design and synthesis of N-(1-(6-(substituted phenyl)-pyridazin-3-yl)-piperidine-3-yl)-amine derivatives as JMJD6 inhibitors

JMJD6 is a member of the JmjC domain-containing family and has been identified as a promising therapeutic target for treating estrogen-induced and triple-negative breast cancer. To develop novel anti-breast cancer agents, we synthesized a class of N-(1-(6-(substituted phenyl)-pyridazine-3-yl)-piperidine-3-yl)-amine derivatives as potential JMJD6 inhibitors. Among them, the anti-cancer compound A29 was an excellent JMJD6 binder (KD = 0.75 ± 0.08 μM). It could upregulate the mRNA and protein levels of p53 and its downstream effectors p21 and PUMA by inhibiting JMJD6. Besides, A29 displayed potent anti-proliferative activities against tested breast cancer cells by the induction of cell apoptosis and cell cycle arrest. Significantly, A29 also promoted a remarkable reduction in tumor growth, with a TGI value of 66.6% (50 mg/kg, i.p.). Taken together, our findings suggest that A29 is a potent JMJD6 inhibitor bearing a new scaffold acting as a promising drug candidate for the treatment of breast cancer.

Design, synthesis and molecular docking simulation of oxindole-based derivatives with dual VEGFR-2 and cholinesterase inhibitory activities

Oxindole-based compounds are deemed to be an interesting scaffold with significant VEGFR-2 and cholinesterase inhibitory properties. Regarding the studies that displayed the adverse effect of cancer chemotherapy on cognitive function which can be long-lasting and negatively affect the quality of life, a series of dispiropyrrolodinyl-oxindoles 4‒27 have been designed and synthesized through a classical 1,3-dipolar cycloaddition reaction. Derivatives 9‒12, 18 and 21 were the best among the tested series that disclosed auspicious mutual inhibitory properties against breast cancer and VEGFR-2 kinase. Whereas compound 12 displayed superior activity than that of the reference drug, tamoxifen. PI-flow cytometry of compound 12 supported the cessation of the cell cycle at the G1/S phase and can be considered as an apoptotic inducer via activation of caspase-3. Moreover, the new chemical entities 17, 18, 21 and 22 exhibited dual-targeted cholinesterase inhibitory properties against AChE and BChE. comparable with donepezil. The possible applicability of the mutual most potent candidates 9‒13, 17, 18, 21 and 22 were supported by the promising safety profiles on normal (non-cancer, VERO) cells. Analogs 18 and 21 exhibited dual VEGFR-2 and cholinesterase inhibitory properties, which can be used as lead compounds for the discovery of prominent dual anti-breast cancer agents and cholinesterase inhibitors. Molecular docking studies of the most promising derivatives within the active sites of VEGFR-2, AChE and BChE enzymes were carried out to confirm the improvement of the binding features through the substituent variation at p-3 and p-4′ of dispiropyrrolodinyl-oxindole as well as the chain length of an alkyl group at indolyl N-1.

A Potential Anticancer Mechanism of Finger Root (Boesenbergia rotunda) Extracts against a Breast Cancer Cell Line.

Breast cancer is the most common type of cancer women suffer from worldwide in 2020 and the 4th leading cause of cancer death. Boesenbergia rotunda is an herb with high potential as an anticancer agent. This study explores the potential bioactive compounds in B. rotunda as anti-breast cancer agents using in silico and in vitro approaches. The in silico study was used for active compound analysis, selection of anticancer compound candidates, prediction of target protein, functional annotation, molecular docking, and molecular dynamics simulation, respectively. The in vitro study was conducted by measurement toxicity, rhodamine 123, and apoptosis assays on T47D cells. Based on the KNApSAcK database, B. rotunda contained 20 metabolites, which are dominated by chalcone and flavonoid groups. Seven of them were predicted to have anticancer activity, namely, sakuranetin, cardamonin, alpinetin, 2S-pinocembrin, 7.4′-dihydroxy-5-methoxyflavanone, 5.6-dehydrokawain, and pinostrobin chalcone. These compounds targeted proteins related to cancer progression pathways such as the PI3K/Akt, FOXO, JAK/STAT, and estrogen signaling pathways. Therefore, these compounds are predicted to inhibit growth and induce apoptosis of cancer cells through their interactions with MMP12, MMP13, CDK4, JAK3, VEGFR1, VEGFR2, and KCNA3. Anticancer activity of B. rotunda through in vitro study confirmed that B. rotunda extract is strong cytotoxic and induces apoptosis of breast cancer cell lines. This study concludes that Boesenbergia rotunda has potency as an anticancer candidate.

Exploring the Potential of Substituted 4-Thiazolidinone Derivatives in the Treatment of Breast Cancer: Synthesis, Biological Screening and In Silico Studies

A series of 4-thiazolidinone conjugates bearing quinoline/indole/furan scaffolds were designed as potential anti-breast cancer agents, synthesized, and investigated for their anti-breast cancer, and anti-oxidant activity. The anticancer activity was performed using MTT assay against breast cancer cell lines such as MCF-7 and MDA-MB-231 and the results demonstrated that most of the compounds were sensitive to cancer cell lines. Compounds GT1, GT2 and GT5 showed remarkable potency against MCF-7 cell lines with IC50 values of 11.64 µM, 11.27 µM and 11.37 µM respectively in comparison to standard drug doxorubicin with IC50 value of 11.80 µM. Compounds GT2 and GT5 exerted higher cytotoxic activity against the MDA-MD-231 cell line with IC50 value of 17.60 µM and 15.09 µM respectively than doxorubicin (IC50: 18.35 µM). The anti-oxidant activity was also performed by DPPH and hydrogen peroxide scavenging assay. Compounds GT2 and GT7 showed higher free radical scavenging activity with IC50 value of 11.39 µM and 11.28 µM respectively against DPPH assay and 10.99 µM and 11.20 µM respectively against hydrogen peroxide assay. The molecular docking study was carried out against estrogen receptor alpha (PDB ID: 4IVY) to identify the mechanism of action of synthesized compounds using molecular docking and molecular dynamics simulation. The results showed that compounds GT1, GT2, and GT5 showed higher docking score −110.922 kcal/mol, −124.618 kcal/mol and-116.029 kcal/mol respectively as compared to reference (doxorubicin) drug (-109.847 kcal/mol). The ADME and toxicity profile was predicated by Schrodinger QikProp program. All the synthesized compounds showed no violation of Lipinski’s rule except GT2. The molecule insight behavior was predicted by using MD simulation. According to in silico and in vitro studies GT1, GT2, and GT5 showed anti-cancerous activity against MCF-7.