Curcuminoid Chalcones: Synthesis and Biological Activity against the Human Colon Carcinoma (Caco-2) Cell Line.

BACKGROUND: There are many current scientific reports on the synthesis of various derivatives modelled on the structure of known small-molecular and natural bioactive compounds. Curcuminoid chalcones are an innovative class of compounds with significant therapeutic potential against various diseases and they perfectly fit into the current trends in the search for new biologically active substances. AIM: The aim of this study was to design and synthesise a series of curcuminoid chalcones. OBJECTIVE: The objective of this scientific paper was to synthesise twelve curcuminoid chalcones and confirm their structures using spectral methods. Additionally, the biological activity of three of the synthesised compounds was evaluated using various assays, and their anticancer properties and toxicity were studied. METHODS: The proposed derivatives were obtained via the Claisen-Schmidt reaction of selected acetophenones and aldehydes in various conditions using both classical methods: the solutions and solvent-free microwave (MW) or ultrasound (US) variants. The most optimal synthetic method for the selected curcuminoid chalcones was the classical Claisen-Schmidt condensation in an alkaline (NaOH) medium. Spectral methods were used to confirm the structures of the compounds. The resazurin reduction assay, caspase-3 activity assay, and RT-qPCR method were performed, followed by measurements of the intracellular reactive oxygen species (ROS) level and the lactate dehydrogenase (LDH) release level. RESULTS: Twelve designed curcuminoid chalcones were successfully synthesized and structurally confirmed by NMR, MS, and IR spectroscopy. Examination of the anticancer activity was carried out for the three most interesting chalcone products. CONCLUSION: The results suggested that compound 3a increased the metabolism and/or proliferation of the human colon carcinoma (Caco-2) cell line, while compounds 3b and 3f showed significant toxicity against the Caco-2 cell line. Overall, the preliminary results suggested that compound 3b exhibited the most favorable anticancer activity.

Curcuminoid Chalcones: Synthesis, Stability, and New Neuroprotective and Sonosensitising Activities.

The primary purpose of this work was to design and obtain a series of curcuminoid chalcone-NSAID hybrid derivatives. The ester-type hybrid compounds with ibuprofen (i), ketoprofen (ii), and naproxen (iii) were obtained in two ways, using the Claisen-Schmidt reaction and the Steglich esterification reaction. The designed molecules were successfully synthesised, and FT-IR, MS, and NMR spectroscopy confirmed their structures. Moreover, the cytotoxic effect of the sonodynamic therapy and the anti-inflammatory, antioxidant, and anticholinergic properties of some curcuminoid chalcones and curcuminoid chalcones hybrids were evaluated. The curcuminoid chalcone derivatives showed promising neuroprotective activity as sonosensitisers for sonodynamic therapy in the studied cell lines. Additionally, the stability of the ester-type hybrid compounds with promising activity was determined. The RP-HPLC method was used to observe the degradation of the tested compounds. Studies have shown that structural isomers of ester-type hybrid compounds (3ai, 3bi) are characterised by a similar susceptibility to degradation factors, i.e., they are extremely unstable in alkaline environments, very unstable in acidic environments, unstable in neutral environments, practically stable in oxidising environments, and photolabile in solutions and in the solid phase. These compounds maintain adequate stability in environment at pH 1.2 and 6.8, which may make them good candidates for developing formulations for oral administration.

Novel Molecular Consortia of Cannabidiol with Nonsteroidal Anti-Inflammatory Drugs Inhibit Emerging Coronaviruses' Entry.

The COVID-19 pandemic provoked a global health crisis and highlighted the need for new therapeutic strategies. In this study, we explore the potential of the molecular consortia of cannabidiol (CBD) and non-steroidal anti-inflammatory drugs (NSAIDs) as novel antiviral dual-target agents against SARS-CoV-2/COVID-19. CBD is a natural compound with a wide range of therapeutic activities, including antiviral and anti-inflammatory properties, while NSAIDs are commonly used to mitigate the symptoms of viral infections. Chemical modifications of CBD with NSAIDs were performed to obtain dual-target agents with enhanced activity against SARS-CoV-2. The synthesised compounds were characterised using spectroscopic techniques. The biological activity of three molecular consortia (CBD-ibuprofen, CBD-ketoprofen, and CBD-naproxen) was evaluated in cell lines transduced with vesicular stomatitis virus-based pseudotypes bearing the SARS-CoV-1 or SARS-CoV-2 spike proteins or infected with influenza virus A/Puerto Rico/8/34. The results showed that some CBD-NSAID molecular consortia have superior antiviral activity against SARS-CoV-1 and SARS-CoV-2, but not against the influenza A virus. This may suggest a potential therapeutic role for these compounds in the treatment of emerging coronavirus infections. Further studies are needed to investigate the efficacy of these compounds in vivo, and their potential use in clinical settings. Our findings provide a promising new approach to combatting current and future viral emergencies.

Curcumin-Triterpene Type Hybrid as Effective Sonosensitizers for Sonodynamic Therapy in Oral Squamous Cell Carcinoma.

Sonodynamic therapy (SDT) is a non-invasive therapeutic modality in cancer treatment that combines low-intensity ultrasound (US) and sonosensitizers. Tumor cells are destroyed through the synergistic effects of ultrasound and a chemical sonosensitizer. This study focused on the synthesis and in vitro evaluation of the sonodynamic effect of natural curcumin, triterpene oleanolic acid, and their semi-synthetic derivatives on tongue cancer SCC-25 and hypopharyngeal FaDu cell lines. The combination of the tested compounds with sonication showed a synergistic increase in cytotoxicity. In the group of oleanolic acid derivatives, oleanoyl hydrogen succinate (6) showed the strongest cytotoxic effect both in the SCC-25 and FaDu cell lines. Comparing curcumin (4) and its pyrazole derivative (5), curcumin showed a better cytotoxic effect on SCC-25 cells, while curcumin pyrazole was more potent on FaDu cells. The highest sonotherapeutic activity, compared to its individual components, was demonstrated by a structural linker mode hybrid containing both curcumin pyrazole-oleanoyl hydrogen succinate units within one complex molecule (7). This study can be beneficial in the context of new perspectives in the search for effective sonosensitizers among derivatives of natural organic compounds.

Synthesis, Cytotoxicity and Molecular Docking of New Hybrid Compounds by Combination of Curcumin with Oleanolic Acid.

Curcumin and oleanolic acid are natural compounds with high potential in medicinal chemistry. These products have been widely studied for their pharmacological properties and have been structurally modified to improve their bioavailability and therapeutic value. In the present study, we discuss how these compounds are utilized to develop bioactive hybrid compounds that are intended to target cancer cells. Using a bifunctional linker, succinic acid, to combine curcumin and triterpenoic oleanolic acid, several hybrid compounds were prepared. Their cytotoxicity against different cancer cell lines was evaluated and compared with the activity of curcumin (the IC50 value (24 h), for MCF7, HeLaWT and HT-29 cancer cells for KS5, KS6 and KS8 compounds was in the range of 20.6-94.4 µM, in comparison to curcumin 15.6-57.2 µM). Additionally, in silico studies were also performed. The computations determined the activity of the tested compounds towards proteins selected due to their similar binding modes and the nature of hydrogen bonds formed within the cavity of ligand-protein complexes. Overall, the curcumin-triterpene hybrids represent an important class of compounds for the development of effective anticancer agents also without the diketone moiety in the curcumin molecule. Moreover, some structural modifications in keto-enol moiety have led to obtaining more information about different chemical and biological activities. Results obtained may be of interest for further research into combinations of curcumin and oleanolic acid derivatives.

The Effect of Oleanolic Acid and Its Four New Semisynthetic Derivatives on Human MeWo and A375 Melanoma Cell Lines.

This study aimed to synthesize four new semisynthetic derivatives of natural oleanolic acid (OA) and, based on an analysis of their cytotoxic and anti-proliferative effects against human MeWo and A375 melanoma cell lines, select those with anti-cancer potential. We also screened the treatment time with the concentration of all four derivatives. We synthesized oxime 2 and performed its acylation with carboxylic acids into new derivatives 3a, 3b, 3c and 3d according to the methods previously described. Colorimetric MTT and SRB assays were used to measure the anti-proliferative and cytotoxic activity of OA and its derivatives 3a, 3b, 3c and 3d against melanoma cells. Selected concentrations of OA, the derivatives, and different time periods of incubation were used in the study. The data were analyzed statistically. The present results revealed the possible anti-proliferative and cytotoxic potential of two selected OA derivatives 3a and 3b, on A375 and MeWo melanoma cells, especially at concentrations of 50 µM and 100 µM at 48 h of incubation (p < 0.05). Further studies will be necessary to analyze the proapoptotic and anti-cancer activities of 3a and 3b against skin and other cancer cells. The bromoacetoxyimine derivative (3b) of OA morpholide turned out to be the most effective against the tested cancer cells.

Biological Activity of Oleanolic Acid Derivatives HIMOXOL and Br-HIMOLID in Breast Cancer Cells Is Mediated by ER and EGFR.

Breast cancer is one of the most frequently observed malignancies worldwide and represents a heterogeneous group of cancers. For this reason, it is crucial to properly diagnose every single case so a specific and efficient therapy can be adjusted. One of the most critical diagnostic parameters evaluated in cancer tissue is the status of the estrogen receptor (ER) and epidermal growth factor receptor (EGFR). Interestingly, the expression of the indicated receptors may be used in a personalized therapy approach. Importantly, the promising role of phytochemicals in the modulation of pathways controlled by ER and EGFR was also demonstrated in several types of cancer. One such biologically active compound is oleanolic acid, but due to poor water solubility and cell membrane permeability that limits its use, alternative derivative compounds were developed. These are HIMOXOL and Br-HIMOLID, which were demonstrated to be capable of inducing apoptosis and autophagy or diminishing the migratory and invasive potential of breast cancer cells in vitro. In our study, we revealed that proliferation, cell cycle, apoptosis, autophagy, and also the migratory potential of HIMOXOL and Br-HIMOLID in breast cancer cells are mediated by ER (MCF7) and EGFR (MDA-MB-231) receptors. These observations make the studied compounds interesting in the context of anticancer strategies.

Social Attitude to COVID-19 and Influenza Vaccinations after the Influenza Vaccination Season and between the Second and Third COVID-19 Wave in Poland, Lithuania, and Ukraine.

The SARS-CoV-2 pandemic affected the entire world and contributed to severe health and economic consequences. A safe and effective vaccine is a tool allowing the pandemic to be controlled. Hence, we aimed to conduct a survey on vaccinations against seasonal influenza and COVID-19 in Poland, Lithuania, and Ukraine. We also evaluated societal attitudes towards influenza and COVID-19 vaccinations. MATERIALS AND METHODS: We conducted the study between December 2020 and May 2021. At the time, the countries subject to the research were between the second and third waves of the COVID-19 pandemic. We used an anonymous and self-designed questionnaire comprised of eleven closed-ended questions and a short socio-demographic section. The questionnaire was administered by direct contact or mainly (due to the COVID-19 pandemic) by e-mail or Facebook. Finally, we included 2753 answers from Poland, 1852 from Ukraine, and 213 from Lithuania. RESULTS: Between 61% (Poland) and 72.9% (Ukraine) of the study participants have never been vaccinated against influenza (p < 0.05). Totals of 67.6% of the respondents in Poland, 73.71% in Lithuania, and 29.5% in Ukraine responded that they want to be vaccinated against COVID-19 (p < 0.05). Vaccine hesitancy was mainly related to worries about its side effects. There were also vaccine non-adopters in the study. In Ukraine, 67% of the respondents were clearly opposed to mandatory COVID-19 vaccines, compared to 41.7% in Poland and 30.99% in Lithuania (p < 0.05). CONCLUSIONS: There are still many people who present vaccine hesitancy or are opposed to vaccines. Thus, societal education about vaccination and the pandemic is crucial. Vaccine hesitancy or refusal might be related to vaccine origin. Shortages of influenza vaccines made it impossible to vaccinate those who were determined to be vaccinated. There is room for discussion of mandatory COVID-19 vaccinations.

The effects of baths and wet wraps with a sweet whey solution on the level of hydration and barrier function of the epidermis.

INTRODUCTION: Sweet whey is known for its various pharmacological uses as an anti-inflammatory and antioxidant agent. This is because whey proteins accelerate the release of bioactive peptides, increase the level of intracellular glutathione and the production of interleukin IL-8. However, the potential skin care effects of whey, especially in its unprocessed state, are still not clear. AIM: To evaluate in vivo the cosmetic features of sweet whey baths and wet wraps on human skin. MATERIAL AND METHODS: Thirteen healthy Caucasian adult females with no dermatological diseases were examined. We used the Courage-Khazaka MPA-9 device to evaluate the effects of sweet whey baths/wet wraps on skin hydration, transepidermal water loss (TEWL) and melanin and erythema index and pH level in human skin. RESULTS: It appeared that bathing in the sweet whey solution significantly improved the barrier function of the skin in comparison with tap water treated control area on the face cheek as well as on the forearm by decreasing the value of transepidermal water loss with statistical significance. Skin hydration was enhanced only on the facial skin. No significant differences concerning other parameters were observed. CONCLUSIONS: We showed that sweet whey may have decreased the TEWL level and fixed the barrier function of epidermis in this way. It seems that a bath solution with sweet whey is well tolerated and may promote local blood circulation without affecting the pH value of the skin.

Oleanolic Acid's Semisynthetic Derivatives HIMOXOL and Br-HIMOLID Show Proautophagic Potential and Inhibit Migration of HER2-Positive Breast Cancer Cells In Vitro.

Approximately 20-30% of the diagnosed breast cancers overexpress the human epidermal growth factor receptor 2 (HER2). This type of cancer is associated with a more aggressive phenotype; thus, there is a need for the discovery of new compounds that would improve the survival in HER2-positive breast cancer patients. It seems that one of the most promising therapeutic cancer strategies could be based on the biological activity of pentacyclic triterpenes' derivatives and the best-known representative of this group, oleanolic acid (OA). The biological activity of oleanolic acid and its two semisynthetic derivatives, methyl 3-hydroxyimino-11-oxoolean-12-en-28-oate (HIMOXOL) and 12α-bromo-3-hydroxyimonoolean-28→13-olide (Br-HIMOLID), was assessed in SK-BR-3 breast cancer cells (HER2-positive). Viability tests, cell cycle assessment, evaluation of apoptosis, autophagy, and adhesion/migration processes were performed using MTT, clonogenic, cytofluorometry, Western blot, and qPCR. Both derivatives revealed higher cytotoxicity in studied breast cancer cells than the maternal compound, OA. They also decreased cell viability, induced autophagy, and (when applied in sub-cytotoxic concentrations) decreased the migration of SK-BR-3 cells.This study is the first to report the cytostatic, proautophagic (mTOR/LC3/SQSTM/BECN1 pathway), and anti-migratory (integrin ß1/FAK/paxillin pathway) activities of HIMOXOL and Br-HIMOLID in HER2-positive breast cancer cells.

Structure and Activity of Pentacyclic Triterpenes Codrugs. A Review.

Triterpenes are a wide and important group of compounds that have several promising pharmacological properties, such as hepatoprotective, anti-inflammatory, anti-HIV, antioxidant, or anticancer activities. Such potent substances can be successfully incorporated in more complex chemical systems e.g. codrugs or pro-drugs that have a better pharmacological profile. The codrug is connected with a drug formation pathway to chemically cohere at least two drug molecules to improve positive therapeutic efficiency or decrease side effects. The codrug can be cleaved in the organism to generate effective compounds previously used as substrates. This article presents an overview of codrugs that consist of pentacyclic triterpene moiety that is chosen as a basic codrug moiety due to their wide range of vital activities and another drug molecule fragment. It was found that triterpenoid codrugs are characterized by a wide range of biological activities. However, most of them have anticancer potency.

Anti-COVID drugs: repurposing existing drugs or search for new complex entities, strategies and perspectives.

At the end of 2019, a novel virus causing severe acute respiratory syndrome to spread globally. There are currently no effective drugs targeting SARS-CoV-2. In this study, based on the analysis of numerous references and selected methods of computational chemistry, the strategy of integrative structural modification of small molecules with antiviral activity into potential active complex molecules has been presented. Proposed molecules have been designed based on the structure of triterpene oleanolic acid and complemented by structures characteristic of selected anti-COVID therapy assisted drugs. Their pharmaceutical molecular parameters and the preliminary bioactivity were calculated and predicted. The results of the above analyses show that among the designed complex substances there are potential antiviral agents directed mainly on SARS-CoV-2.

Oleanolic acid oxime derivatives and their conjugates with aspirin modulate the NF-κB-mediated transcription in HepG2 hepatoma cells.

The aim of this study was to evaluate the effect of new oleanolic acid oxime (OAO) derivatives and their conjugates with aspirin (ASP) on the expression and activation of NF-κB in human hepatoma HepG2 cells. OAO derivatives showed a stronger cytotoxic effect against HepG2 cells compared with their conjugates with aspirin. Moreover, conjugation of OAO with ASP led to enhanced downregulation of NF-κB expression and activation. Among the hybrids with ASP, compounds: 19, 3-(2-acetoxy)benzoyloxyiminoolean-12-en-28-oic acid morpholide and 13, 3-(2-acetoxy)benzoyloxyiminoolean-12-en-28-oic acid methyl ester, differing, respectively, in morpholide and methyl ester groups at the C-17 position of oleanolic acid (OA) molecule were the most efficient. COX-2 transcript and protein levels were also diminished after treatment with these compounds. The results of this study indicate that the new derivatives of OAO and particularly their conjugates with ASP, downregulate the expression of COX-2 in HepG2 cells by modulating the NF-κB signaling pathway and suggest their potential application in the prevention of liver inflammation and cancer.

Microwave (MW), Ultrasound (US) and Combined Synergic MW-US Strategies for Rapid Functionalization of Pharmaceutical Use Phenols.

Increasingly stringent regulations aimed at protection of the natural environment have stimulated the search for new synthetic methodologies in organic and medicinal chemistry having no or minimum harmful effect. An interesting approach is the use of alternative activation factors, microwaves (MW) or ultrasounds (US) and also their cross-combination, which has been tested in the fast and efficient creation of new structures. At present, an easy and green hybrid strategy ("Lego" chemistry) is generally recommended for the design of new substances from different chemistry building blocks. Often, selected biologically active components with specific chemical reactivities are integrated by a suitably designed homo- or heterodifunctional linker that modifies the functionality of the starting structure, allowing easy covalent linkage to another molecule. In this study, a fast introduction of heterodifunctional halogenoacidic linker to selected mono-, di- and triphenolic active substances, allowing their functionalization, was investigated. Nucleophilic substitution reaction was chosen to produce final ethers with the reactive carboxylic group from phenols. The functionalization was performed using various green factors initiating and supporting the chemical reactions (MW, US, MW-US). The benefits of the three green supporting methods and different conditions of reactions were analyzed and compared with the results of the reaction performed by conventional methods.

The Structure and Activity of Double-Nitroimidazoles. A Mini-Review.

Many interesting applications have been found for nitroimidazoles as therapeutic agents. Among others, some of these compounds can radiosensitize hypoxic tumor cells. The introduction of a second nitroimidazole ring to the molecule can improve the level of its pharmacological effect. The aim of this article is to overview the literature concerning active compounds that contain two nitroimidazole moieties in their structures.

Multidirectional Efficacy of Biologically Active Nitro Compounds Included in Medicines.

The current concept in searching for new bioactive products, including mainly original active substances with potential application in pharmacy and medicine, is based on compounds with a previously determined structure, well-known properties, and biological activity profile. Nowadays, many commonly used drugs originated from natural sources. Moreover, some natural materials have become the source of leading structures for processing further chemical modifications. Many organic compounds with great therapeutic significance have the nitro group in their structure. Very often, nitro compounds are active substances in many well-known preparations belonging to different groups of medicines that are classified according to their pharmacological potencies. Moreover, the nitro group is part of the chemical structure of veterinary drugs. In this review, we describe many bioactive substances with the nitro group, divided into ten categories, including substances with exciting activity and that are currently undergoing clinical trials.

Molecular Consortia-Various Structural and Synthetic Concepts for More Effective Therapeutics Synthesis.

The design and discovery of novel drug candidates are the initial and most probably the crucial steps in the drug development process. One of the tasks of medicinal chemistry is to produce new molecules that have a desired biological effect. However, even today the search for new pharmaceuticals is a very complicated process that is hard to rationalize. Literature provides many scientific reports on future prospects of design of potentially useful drugs. Many trends have been proposed for the design of new drugs containing different structures (dimers, heterodimers, heteromers, adducts, associates, complexes, biooligomers, dendrimers, dual-, bivalent-, multifunction drugs and codrugs, identical or non-identical twin drugs, mixed or combo drugs, supramolecular particles and various nanoindividuals. Recently much attention has been paid to different strategies of molecular hybridization. In this paper, various molecular combinations were described e.g., drug-drug or drug-non-drug combinations which are expressed in a schematic multi-factor form called a molecular matrix, consisting of four factors: association mode, connection method, and the number of elements and linkers. One of the most popular trends is to create small-small molecule combinations such as different hybrids, codrugs, drug-drug conjugates (DDCs) and small-large molecule combinations such as antibody-drug conjugates (ADCs), polymer-drug conjugates (PDCs) or different prodrugs and macromolecular therapeutics. A review of the structural possibilities of active framework combinations indicates that a wide range of potentially effective novel-type compounds can be formed. What is particularly important is that new therapeutics can be obtained in fast, efficient, and selective methods using current trends in chemical synthesis and the design of drugs such as the "Lego" concept or rational green approach.

1,2-Benzoxathiin-4(3H)-one 2,2-dioxide - new enol nucleophile in three-component interaction with benzaldehydes and active methylene nitriles.

The reactivity of 1,2-benzoxathiin-4(3H)-one 2,2-dioxide was studied in multicomponent type reactions for the first time, namely, in a three-component interaction with active methylene nitriles and aromatic aldehydes in order to construct condensed 2-amino-4H-pyran derivatives. The reaction outcome strongly depended on the nature of an active methylene nitrile and an arenecarbaldehyde. Application of malononitrile resulted in novel 2-amino-4-aryl-4H-pyrano[3,2-c][1,2]benzoxathiine-3-carbonitrile 5,5-dioxides in most cases, whereas the utilization of ethyl cyanoacetate resulted in a complex mixture of products. In the last case, three different products were isolated depending on the arenecarbaldehyde used, namely ethyl 2-amino-4-aryl-4H-pyrano[3,2-c][1,2]benzoxathiine-3-carboxylate 5,5-dioxides, ethyl 2-cyano-3-arylacrylates, and salts of 3,3'-(arylmethylene)bis(4-hydroxybenzo[e][1,2]oxathiine 2,2-dioxides). Attempts to obtain separately ethyl 2-amino-4-aryl-4H-pyrano[3,2-c][1,2]benzoxathiine-3-carboxylate 5,5-dioxides enabled us to propose reaction pathways leading to these products. The salts were obtained for the first time. The preparative method for the synthesis of triethylammonium salts of 3,3'-(arylmethylene)bis(4-hydroxybenzo[e][1,2]oxathiine 2,2-dioxides) was proposed by the direct interaction of 1,2-benzoxathiin-4(3H)-one 2,2-dioxide with arenecarbaldehydes. The application of ammonium acetate as a catalyst allowed us to synthesize 7-aryl-7,14-dihydrobenzo[5,6][1,2]oxathiino[4,3-b]benzo[5,6][1,2]oxathiino[3,4-e]pyridine 6,6,8,8-tetraoxides containing a novel heterocyclic system. These facts, combined with our past investigations, allowed us to assert that the reactivity of enol nucleophiles that include the COCH2SO2X fragment has not been reported previously.

Pharmaceutical applications of graphene.

Nowadays, dynamic development in nanotechnological sciences is observed. Nanoparticles are frequently used in medicine and pharmacy as delivery systems for different kinds of active substances. One of the latest developed substances, with an unusually wide scope of utility, is graphene. The ways of its use in different fields of industry, not only pharmaceutical and medical, have been a subject of study for many research groups since the moment of its development in 2004. Graphene in pure form is highly hydrophobic. However, the presence of defects on its surface allows chemical modifications to be made, e.g. introduction of oxygen groups by covalent bonding. Also, non-covalent modifications are extensively used, including van der Waals forces, hydrogen bonding, coordination bonds, electrostatic and π-π stacking interactions. Due to the large surface area, graphene can be used in combination therapy, consisting in simultaneous administration of two or more pharmacologically active agents. Another interesting approach is gene therapy. Application of the PEI-graphene oxide system increased the efficacy of transfection. Possibilities of graphene and graphene oxide are not limited to their use as active substance delivery systems. These compounds by themselves were also found to be bacteriostatic and antibacterial agents.

Semisynthetic oleanane triterpenoids inhibit migration and invasion of human breast cancer cells through downregulated expression of the ITGB1/PTK2/PXN pathway.

This paper reports a study on the role of two synthetic derivatives of oleanolic acid (OA), HIMOXOL and Br-HIMOLID, in the regulation of cell migration and invasion and the underlying molecular mechanisms of breast cancer cells. The effect of the compounds on four breast cancer cell lines (MCF7, MDA-MB-231, MDA-MB-468, and T-47D) and also on noncancerous breast cells, MCF-12A, was reported. The compounds had no effect on the migration of MCF-12A cells. However, both the derivatives revealed a higher cytotoxicity than the maternal compound OA, and in sub-cytotoxic concentrations, they decreased the migration of MCF7, MDA-MB-231, and MDA-MB-468 breast cancer cells and also the invasion of MCF7 and MDA-MB-231 cells; although, the derivatives had no effect on the migration and invasion of T-47D cells. Both the derivatives of OA inhibited the cell migratory and invasive abilities of breast cancer cells by downregulating the expressions of ITGB1, PTK2, and PXN genes and by decreasing the phosphorylation status and the level of its respective proteins (integrin ß1, FAK, and paxillin, respectively). This study is the first to report the antimigratory and anti-invasive activities of HIMOXOL and Br-HIMOLID in breast cancer cells.