Colorectal anticancer activity of a novel class of triazolic triarylmethane derivatives.

Triarylmethanes and triazoles constitute privileged structures extensively used in drug discovery programs. In this work, 12 novel triarylmethanes linked to a triazole ring were designed, synthesized, and chemically characterized aiming to target colorectal cancer. The synthetic strategy for triarylmethanes mono- and bi-substituted by a functionalized triazole ring involved a 1,3-dipolar cycloaddition. A preliminary screening in human colorectal cancer cells (HT-29 and HCT116) and murine primary fibroblasts (L929) allowed the selection of the best candidate 9b based on its high inhibition of cancer cell proliferation with an IC50 of 11 µM on HT-29 and 14 µM on HCT116 and its non-cytotoxic effects on murine fibroblasts (<100 µM). A deep mechanistic study on various pathways showed that compound 9b induces caspase-3 cleavage, and its inhibitory effect on PARP activity is correlated with the increase of DNA fragmentation in cancer cells. Moreover, 9b induced apoptosis promoted by the inhibition of anti-apoptotic cell survival signaling pathways demonstrated via the downregulation of phosphorylated Akt and ERK proteins. Finally, the predicted binding modes of compounds 8c and 9b to five potential biological targets (i.e., AKT, ERK-1 and ERK-2, PARP and caspase-3) was evaluated using molecular modeling, and the predictions of the SuperPred webserver identified ERK2 as the most remarkable target. Also predicted in silico, 9b displayed appropriate drug-likeness and good absorption, distribution, metabolism and excretion (ADME) profiles.

Ursolic Acid's Alluring Journey: One Triterpenoid vs. Cancer Hallmarks.

Cancer is a multifactorial disease characterized by various hallmarks, including uncontrolled cell growth, evasion of apoptosis, sustained angiogenesis, tissue invasion, and metastasis, among others. Traditional cancer therapies often target specific hallmarks, leading to limited efficacy and the development of resistance. Thus, there is a growing need for alternative strategies that can address multiple hallmarks concomitantly. Ursolic acid (UA), a naturally occurring pentacyclic triterpenoid, has recently emerged as a promising candidate for multitargeted cancer therapy. This review aims to summarize the current knowledge on the anticancer properties of UA, focusing on its ability to modulate various cancer hallmarks. The literature reveals that UA exhibits potent anticancer effects through diverse mechanisms, including the inhibition of cell proliferation, induction of apoptosis, suppression of angiogenesis, inhibition of metastasis, and modulation of the tumor microenvironment. Additionally, UA has demonstrated promising activity against different cancer types (e.g., breast, lung, prostate, colon, and liver) by targeting various cancer hallmarks. This review discusses the molecular targets and signaling pathways involved in the anticancer effects of UA. Notably, UA has been found to modulate key signaling pathways, such as PI3K/Akt, MAPK/ERK, NF-κB, and Wnt/ß-catenin, which play crucial roles in cancer development and progression. Moreover, the ability of UA to destroy cancer cells through various mechanisms (e.g., apoptosis, autophagy, inhibiting cell growth, dysregulating cancer cell metabolism, etc.) contributes to its multitargeted effects on cancer hallmarks. Despite promising anticancer effects, this review acknowledges hurdles related to UA's low bioavailability, emphasizing the need for enhanced therapeutic strategies.

Natural Chalcones and Derivatives in Colon Cancer: Pre-Clinical Challenges and the Promise of Chalcone-Based Nanoparticles.

Colon cancer poses a complex and substantial global health challenge, necessitating innovative therapeutic approaches. Chalcones, a versatile class of compounds with diverse pharmacological properties, have emerged as promising candidates for addressing colon cancer. Their ability to modulate pivotal signaling pathways in the development and progression of colon cancer makes them invaluable as targeted therapeutics. Nevertheless, it is crucial to recognize that although chalcones exhibit promise, further pre-clinical studies are required to validate their efficacy and safety. The journey toward effective colon cancer treatment is multifaceted, involving considerations such as optimizing the sequencing of therapeutic agents, comprehending the resistance mechanisms, and exploring combination therapies incorporating chalcones. Furthermore, the integration of nanoparticle-based drug delivery systems presents a novel avenue for enhancing the effectiveness of chalcones in colon cancer treatment. This review delves into the mechanisms of action of natural chalcones and some derivatives. It highlights the challenges associated with their use in pre-clinical studies, while also underscoring the advantages of employing chalcone-based nanoparticles for the treatment of colon cancer.

The Promise of Piperine in Cancer Chemoprevention.

Cancer, characterized by the unregulated growth and dissemination of malignantly transformed cells, presents a significant global health challenge. The multistage process of cancer development involves intricate biochemical and genetic alterations within target cells. Cancer chemoprevention has emerged as a vital strategy to address this complex issue to mitigate cancer's impact on healthcare systems. This approach leverages pharmacologically active agents to block, suppress, prevent, or reverse invasive cancer development. Among these agents, piperine, an active alkaloid with a wide range of therapeutic properties, including antioxidant, anti-inflammatory, and immunomodulatory effects, has garnered attention for its potential in cancer prevention and treatment. This comprehensive review explores piperine's multifaceted role in inhibiting the molecular events and signaling pathways associated with various stages of cancer development, shedding light on its promising prospects as a versatile tool in cancer chemoprevention. Furthermore, the review will also delve into how piperine enhances the effectiveness of conventional treatments such as UV-phototherapy and TRAIL-based therapy, potentially synergizing with existing therapeutic modalities to provide more robust cancer management strategies. Finally, a crucial perspective of the long-term safety and potential side effects of piperine-based therapies and the need for clinical trials is also discussed.

The Effect of Photosensitizer Metalation Incorporated into Arene-Ruthenium Assemblies on Prostate Cancer.

Prostate cancer is the second most common cancer for men and a major health issue. Despite treatments, a lot of side effects are observed. Photodynamic therapy is a non-invasive method that uses photosensitizers and light to induce cell death through the intramolecular generation of reactive oxygen species, having almost no side effects. However, some of the PSs used in PDT show inherent low solubility in biological media, and accordingly, functionalization or vectorization is needed to ensure internalization. To this end, we have used arene-ruthenium cages in order to deliver PSs to cancer cells. These metalla-assemblies can host PSs inside their cavity or be constructed with PS building blocks. In this study, we wanted to determine if the addition of metals (Mg, Co, Zn) in the center of these PSs plays a role. Our results show that most of the compounds induce cytotoxic effects on DU 145 and PC-3 human prostate cancer cells. Localization by fluorescence confirms the internalization of the assemblies in the cytoplasm. An analysis of apoptotic processes shows a cleavage of pro-caspase-3 and poly-ADP-ribose polymerase, thus leading to a strong induction of DNA fragmentation. Finally, the presence of metals in the PS decreases PDT's effect and can even annihilate it.

Polyphenol-Based Nanoparticles: A Promising Frontier for Enhanced Colorectal Cancer Treatment.

Colorectal cancer (CRC) poses a significant challenge in healthcare, necessitating the exploration of novel therapeutic strategies. Natural compounds such as polyphenols with inherent anticancer properties have gained attention as potential therapeutic agents. This review highlights the need for novel therapeutic approaches in CRC, followed by a discussion on the synthesis of polyphenols-based nanoparticles. Various synthesis techniques, including dynamic covalent bonding, non-covalent bonding, polymerization, chemical conjugation, reduction, and metal-polyphenol networks, are explored. The mechanisms of action of these nanoparticles, encompassing passive and active targeting mechanisms, are also discussed. The review further examines the intrinsic anticancer activity of polyphenols and their enhancement through nano-based delivery systems. This section explores the natural anticancer properties of polyphenols and investigates different nano-based delivery systems, such as micelles, nanogels, liposomes, nanoemulsions, gold nanoparticles, mesoporous silica nanoparticles, and metal-organic frameworks. The review concludes by emphasizing the potential of nanoparticle-based strategies utilizing polyphenols for CRC treatment and highlights the need for future research to optimize their efficacy and safety. Overall, this review provides valuable insights into the synthesis, mechanisms of action, intrinsic anticancer activity, and enhancement of polyphenols-based nanoparticles for CRC treatment.

Shining a Light on Prostate Cancer: Photodynamic Therapy and Combination Approaches.

Prostate cancer is a major health concern worldwide, and current treatments, such as surgery, radiation therapy, and chemotherapy, are associated with significant side effects and limitations. Photodynamic therapy (PDT) is a promising alternative that has the potential to provide a minimally invasive and highly targeted approach to treating prostate cancer. PDT involves the use of photosensitizers (PSs) that are activated by light to produce reactive oxygen species (ROS), which can induce tumor cell death. There are two main types of PSs: synthetic and natural. Synthetic PSs are classified into four generations based on their structural and photophysical properties, while natural PSs are derived from plant and bacterial sources. Combining PDT with other therapies, such as photothermal therapy (PTT), photoimmunotherapy (PIT), and chemotherapy (CT), is also being explored as a way to improve its efficacy. This review provides an overview of conventional treatments for prostate cancer, the underlying principles of PDT, and the different types of PSs used in PDT as well as ongoing clinical studies. It also discusses the various forms of combination therapy being explored in the context of PDT for prostate cancer, as well as the challenges and opportunities associated with this approach. Overall, PDT has the potential to provide a more effective and less invasive treatment option for prostate cancer, and ongoing research is aimed at improving its selectivity and efficacy in clinical settings.

Antitumoral activity of Caralluma europaea on colorectal and prostate cancer cell lines.

Caralluma europaea is a medicinal plant used in Moroccan popular medicine, which has been employed as a remedy attributed to its anti-inflammatory, antipyretic, antinociceptive, antidiabetic, neuroprotective, and antiparasitic properties. The aim of the present study was to investigate the antitumor activity of both the methanolic and aqueous extract of C. europaea. The effects of increasing concentrations of aqueous and methanolic extracts on human colorectal cancer HT-29 and HCT116 cell lines and human prostate cancer PC3 and DU145 cell lines were examined on cell proliferation using MTT assay and cell cycle analysis. The induction of apoptosis was also assessed by determining protein expression of caspase-3 and poly-ADP-ribose polymerase (PARP) cleavage by western blot. The methanolic extract of C. europaea exerted significant antiproliferative effects on HT-29 (IC50 values 73 µg/ml), HCT116 (IC50 values 67 µg/ml), PC3 (IC50 values 63 µg/ml) and DU145 cells (IC50 values 65 µg/ml) after 48 hr treatment. Further, incubation with methanolic extract of C. europaea induced cell cycle arrest in G1 phase and an apoptotic process for all treated cell lines. In conclusion, the present results suggest that C. europaea, exhibited that these natural compounds are significant apoptosis inducers which may have considerable potential for development of effective natural product anticancer agents.

Dimethyl Sulfoxide: A Bio-Friendly or Bio-Hazard Chemical? The Effect of DMSO in Human Fibroblast-like Synoviocytes.

The effect of dimethyl sulfoxide (DMSO) in rheumatoid arthritis (RA) human fibroblast-like synoviocytes (FLSs) has been studied on five different samples harvested from the joints (fingers, hands and pelvis) of five women with RA. At high concentrations (>5%), the presence of DMSO induces the cleavage of caspase-3 and PARP-1, two phenomena associated with the cell death mechanism. Even at a 0.5% concentration of DMSO, MTT assays show a strong toxicity after 24 h exposure (≈25% cell death). Therefore, to ensure a minimum impact of DMSO on RA FLSs, our study shows that the concentration of DMSO has to be below 0.05% to be considered safe.

Ruthenium-based assemblies incorporating tetrapyridylporphyrin panels: a photosensitizer delivery strategy for the treatment of rheumatoid arthritis by photodynamic therapy.

Ruthenium-based assemblies containing tetrapyridylporphyrins (TPyP) in their structure have been evaluated as photosensitizers (PS) to treat rheumatoid arthritis (RA) by photodynamic therapy (PDT). TPyP is useless by itself as a PS due to its low solubility in biological media, however, incorporated in metallacages it can be internalized in cells. The study shows a cellular antiproliferative activity in fibroblast-like synoviocyte (FLS) in the lower nanomolar range in the presence of light, and no dark toxicity at 1 µM concentration, thus having an excellent photoactivity index. The presence of diamagnetic (Zn2+) and paramagnetic (Co2+) metals in the center of TPyP impairs the effectiveness of PDT, showing no (Co) or reduced (Zn) photoactivity. A total of five metallacages with different structural characteristics have been evaluated, and our results suggest that the incorporation of PS in metalla-assemblies is not only an elegant method to increase solubility in biological media for TPyP but also appears to be an efficient hybrid system to treat RA by PDT.

Novel Set of Diarylmethanes to Target Colorectal Cancer: Synthesis, In Vitro and In Silico Studies.

Distinctive structural, chemical, and physical properties make the diarylmethane scaffold an essential constituent of many active biomolecules nowadays used in pharmaceutical, agrochemical, and material sciences. In this work, 33 novel diarylmethane molecules aiming to target colorectal cancer were designed. Two series of functionalized olefinic and aryloxy diarylmethanes were synthesized and chemically characterized. The synthetic strategy of olefinic diarylmethanes involved a McMurry cross-coupling reaction as key step and the synthesis of aryloxy diarylmethanes included an O-arylation step. A preliminarily screening in human colorectal cancer cells (HT-29 and HCT116) and murine primary fibroblasts (L929) allowed the selection, for more detailed analyses, of the three best candidates (10a, 10b and 12a) based on their high inhibition of cancer cell proliferation and non-toxic effects on murine fibroblasts (<100 µM). The anticancer potential of these diarylmethane compounds was then assessed using apoptotic (phospho-p38) and anti-apoptotic (phospho-ERK, phospho-Akt) cell survival signaling pathways, by analyzing the DNA fragmentation capacity, and through the caspase-3 and PARP cleavage pro-apoptotic markers. Compound 12a (2-(1-(4-methoxyphenyl)-2-(4-(trifluoromethyl)phenyl) vinyl) pyridine, Z isomer) was found to be the most active molecule. The binding mode to five biological targets (i.e., AKT, ERK-1 and ERK-2, PARP, and caspase-3) was explored using molecular modeling, and AKT was identified as the most interesting target. Finally, compounds 10a, 10b and 12a were predicted to have appropriate drug-likeness and good Absorption, Distribution, Metabolism and Excretion (ADME) profiles.

Porphyrin/Chlorin Derivatives as Promising Molecules for Therapy of Colorectal Cancer.

Colorectal cancer (CRC) is a leading cause of cancer-related death. The demand for new therapeutic approaches has increased attention paid toward therapies with high targeting efficiency, improved selectivity and few side effects. Porphyrins are powerful molecules with exceptional properties and multifunctional uses, and their special affinity to cancer cells makes them the ligands par excellence for anticancer drugs. Porphyrin derivatives are used as the most important photosensitizers (PSs) for photodynamic therapy (PDT), which is a promising approach for anticancer treatment. Nevertheless, the lack of solubility and selectivity of the large majority of these macrocycles led to the development of different photosensitizer complexes. In addition, targeting agents or nanoparticles were used to increase the efficiency of these macrocycles for PDT applications. On the other hand, gold tetrapyrrolic macrocycles alone showed very interesting chemotherapeutic activity without PDT. In this review, we discuss the most important porphyrin derivatives, alone or associated with other drugs, which have been found effective against CRC, as we describe their modifications and developments through substitutions and delivery systems.

Evaluation of Ruthenium-Based Assemblies as Carriers of Photosensitizers to Treat Rheumatoid Arthritis by Photodynamic Therapy.

For the first time, ruthenium-based assemblies have been used as carriers for photosensitizers in the treatment of rheumatoid arthritis by photodynamic therapy (PDT). These metallacages are totally soluble in physiological media and can transport photosensitizers (PS) in their cavity. After an incubation period, the PS is released in the cytoplasm and irradiation can take place. This strategy allows photosensitizers with low or null solubility in biological media to be evaluated as PDT agents in rheumatoid arthritis. The systems in which 21H,23H-porphine and 29H,31H-phthalocyanine are encapsulated show excellent photocytotoxicity and no toxicity in the dark. On the other hand, systems in which metalated derivatives such as Mg(II)-porphine and Zn(II)-phthalocyanine are used show good photocytotoxicity, but to a lesser extent than the previous two. Furthermore, the presence of Zn(II)-phthalocyanine significantly increases the toxicity of the system. Overall, fifteen different host-guest systems have been evaluated, and based on the results obtained, they show high potential for treating rheumatoid arthritis by PDT.

Involvement of autophagy in diosgenin­induced megakaryocyte differentiation in human erythroleukemia cells.

Natural agents have been used to restart the process of differentiation that is inhibited during leukemic transformation of hematopoietic stem or progenitor cells. Autophagy is a housekeeping pathway that maintains cell homeostasis against stress by recycling macromolecules and organelles and plays an important role in cell differentiation. In the present study, an experimental model was established to investigate the involvement of autophagy in the megakaryocyte differentiation of human erythroleukemia (HEL) cells induced by diosgenin [also known as (25R)­Spirosten­5­en­3b­ol]. It was demonstrated that Atg7 expression was upregulated from day 1 of diosgenin­induced differentiation and was accompanied by a significant elevation in the conversion of light chain 3 A/B (LC3­A/B)­I to LC3­A/B­II. Autophagy was modulated before or after the induction of megakaryocyte differentiation using 3­methyladenine (3­MA, autophagy inhibitor) and metformin (Met, autophagy initiation activator). 3­MA induced a significant accumulation of the LC3 A/B­II form at day 8 of differentiation. It was revealed that 3­MA had a significant repressive effect on the nuclear (polyploidization) and membrane glycoprotein V [(GpV) expression] maturation. On the other hand, autophagy activation increased GpV genomic expression, but did not change the nuclear maturation profile after HEL cells treatment with Met. It was concluded that autophagy inhibition had a more prominent effect on the diosgenin­differentiated cells than autophagy activation.

Synthesis and biological evaluation of chalcone-polyamine conjugates as novel vectorized agents in colorectal and prostate cancer chemotherapy.

The aim of this study was to synthesize chalcone-polyamine conjugates in order to enhance bioavailability and selectivity of chalcone core towards cancer cells, using polyamine-based vectors. Indeed, it is well-known that polyamine transport system is upregulated in tumor cells. 3',4,4',5'-tetramethoxychalcone was selected as parent chalcone since it was found to be an efficient anti-proliferative agent on various cancer cells. A series of five chalcone-polyamine conjugates was obtained using the 4-bromopropyloxy-3',4',5'-trimethoxychalcone as a key intermediate. Chalcone core and polyamine tails were fused through an amine bond. These conjugates were found to possess a marked in vitro antiproliferative effect against colorectal (HT-29 and HCT-116) and prostate cancer (PC-3 and DU-145) cell lines. The most active conjugate (compound 8b) was then chosen for further biological evaluations to elucidate mechanisms responsible for its antiproliferative activity. Investigations on cell cycle distribution revealed that this conjugate can prevent the proliferation of human colorectal and prostate cancer cells by blocking the cell cycle at the G1 and G2 phase, respectively. Flow cytometry analysis revealed a sub-G1 peak, characteristic of apoptotic cell population and our inquiries highlighted apoptosis induction at early and later stages through several pro-apoptotic markers. Therefore, this chalcone-N1-spermidine conjugate could be considered as a promising agent for colon and prostatic cancer adjuvant therapy.

Design and synthesis of zinc protoporphyrin IX-adamantane/cyclodextrin/cellulose nanocrystals complexes for anticancer photodynamic therapy.

Two protoporphyrin IX (PpIX) adamantane derivatives were synthesized and then metallated with zinc. The Zn-PpIX derivatives, exhibiting a high singlet oxygen quantum yield, were tested for their photodynamic activity against the HT-29 cell line. In order to enhance their water-solubility and their cellular bioavailability, these photosensitizers were encapsulated into the hydrophobic cavity of cyclodextrins (CD) previously attached to cellulose nanocrystals (CNCs) via electrostatic interactions. Under illumination, the encapsulated adamantanyl-porphyrins exerted an enhanced in vitro cytotoxicity, as compared with the corresponding free photosensitizers.

Ibuprofen-loaded calcium phosphate granules: A new bone substitute for local relieving symptoms of osteoarthritis.

Musculoskeletal diseases often demand a drug treatment at the specific site of injury or defect site. In this context, the use of calcium phosphates is attractive as it allows both the bone substitution and the local delivery of a drug substance. In this work, we present a drug delivery device that combines calcium phosphate bioceramic granules and ibuprofen, a widely used anti-inflammatory drug. After verifying in vitro biocompatibility of the ibuprofen-loaded calcium phosphate granules on murine preosteoblastic cells (MC3T3), we evaluated in vitro efficiency of the drug substance released from the bioceramic using rheumatoid arthritis synoviocytes. Our data document that ibuprofen-loaded calcium phosphate granules reduced inflammatory response and increased apoptosis of synoviocytes. In vivo study showed that both unloaded, and ibuprofen-loaded calcium phosphate granules induced a progressive osteogenesis, but in the case of ibuprofen-loaded implants, bone ingrowth was more limited in first weeks. However, as far as concerns inflammation, while unloaded granules showed inflammation up to 4 weeks, ibuprofen loaded granules did not show any significant inflammation. Ibuprofen concentration determination in blood samples showed that a very small amount of the drug reached the general circulation which render this drug delivery system suitable for both bone substitution and reduction of inflammation at the implantation site. Thus, this new drug carrier could be used to locally relieve inflammatory bone diseases symptoms including rheumatoid arthritis but, beyond this study, this kind of granules could be considered for the delivery of therapeutic agents such as antibiotic, analgesic or anticancer drugs.

Metformin and Probiotics in the Crosstalk between Colitis-Associated Colorectal Cancer and Diabetes in Mice.

The co-occurrence of colorectal cancer (CRC) and diabetes mellitus along with inflammation and dismicrobism has been frequently reported. Several studies shed light on the antioncogenic potential of metformin on colorectal carcinogenesis. This study aimed to demonstrate that metformin in association with probiotics acts in a synergic effect in breaking the crosstalk, thus inhibiting CRC progression, improving diabetes, and reducing inflammation. Ninety-six male Balb/c mice, 6-8 weeks old, were divided into 16 control and experimental groups to assess the effect of the different treatments and combinations at the clinical, histological, and molecular levels. Metformin and probiotics showed beneficial outcomes on CRC and diabetes, alone and most importantly in combination. Their effects were exerted by inhibiting the inflammatory process whereby a downregulation of IL-6 and TNF-α as well as oxidative stress were depicted. The characterization of the effects of probiotics and metformin on CRC and diabetes sheds light on the role of inflammation and microbiota in this crosstalk. Deciphering the downstream signaling pathways elicited by these compounds will help in developing new effective targeted treatment modalities.

Growth Inhibitory and Pro-Apoptotic Effects of Ornamental Pomegranate Extracts in Du145 Human Prostate Cancer Cells.

Aims: Prostate cancer is the most common form of cancer in the male. Epidemiological studies have associated increased cancer incidence with reduced consumption of fruit and vegetables. This study was aimed to investigate the influence of dwarf pomegranate extracts (peel, juice, and seeds oil) on the proliferation and apoptosis of human prostate androgen-independent cell line DU145. Methods: The cell viability was determined by the MTT assay. Morphological changes are detected by light microscopy. The ELISA assay is used to evaluate the nuclear DNA fragmentation and western Blot to detect the expression of apoptosis-associated proteins including poly-ADP-ribose polymerase (PARP) and cyclooxygenase-2 (COX-2). Results: The three tested extracts exhibited a dose-response cytotoxic effect and antiproliferative action on DU145 cell line and induce morphological changes. The dose of each extract required to inhibit cell proliferation by 50% (IC50) was 0.12, 0.36, and 0.42 mg/mL, respectively, for seeds oil, juice, and peel. The three extracts could also induce prostate cancer cell apoptosis by an increase of DNA fragmentation, PARP cleavage, and inhibition of the COX-2 expression. The strongest pro-apoptotic effect was shown after peel treatment. Conclusion: Dwarf pomegranate extracts exhibited potent growth inhibitory activities in human prostate cancer cells (DU145), which appear to be mediated by a pro-apoptotic mechanism.

Pegylated triarylmethanes: Synthesis, antimicrobial activity, anti-proliferative behavior and in silico studies.

We describe herein the synthesis, characterization and biological studies of novel PEGylated triarylmethanes. Non-symmetrical and symmetrical triarylmethanes series have been synthesized by Friedel-Crafts hydroxyalkylation or directly from bisacodyl respectively followed by a functionalization with PEG fragments in order to increase bioavailability and biological effectiveness. The antimicrobial activity was investigated against Gram-positive and Gram-negative foodborne pathogens and against Candida albicans, an opportunistic pathogenic yeast. The anti-biocidal activity was also studied using Staphylococcus aureus as a reference bacterium. Almost all PEGylated molecules displayed an antifungal activity comparable with fusidic acid with MIC values ranging from 6.25 to 50 µg/mL. Compounds also revealed a promising antibiofilm activity with biofilm eradication percentages values above 80% for the best molecules (compounds 4d and 7). Compounds 7 and 8b showed a modest antiproliferative activity against human colorectal cancer cell lines HT-29. Finally, in silico molecular docking studies revealed DHFR and DNA gyrase B as potential anti-bacterial targets and in silico predictions of ADME suggested adequate drug-likeness profiles for the synthetized triarylmethanes.