The cytotoxic, genotoxic and mitotoxic effects of Atractylis gummifera extract in vitro.

Background: The Mediterranean thistle Atractylis gummifera L. (Asteraceae; AG) has diterpenoid glucosides; atractyloside and carboxyatractyloside that interact with mitochondrial protein adenine nucleotide translocator (ANT) and resulted in ATP inhibition. Despite its well-known toxicity, acute poisonings still occur with this plant. Although most symptoms are attributed to ANT and diterpenoids interaction, in-depth investigation of the effects of AG extract on various cellular processes has not been performed. Objective/method: We tested in vitro induction of mitochondrial permeability transition pore (MPTP) opening in bovine liver mitochondria and evaluated its cytotoxicity and genotoxicity using Allium cepa test. Cell division, mitotic index (MI) and total chromosomal and mitotic aberrations (TAs), that all seem potentially affected by ATP shortage, were studied in root cells of Allium cepa exposed to Atractylis gummifera extract. Results: With the two different doses of two purified AG fractions, stronger induction of MPTP was observed compared to the induction with the standard pure atracyloside. Aqueous AG extract exerted inhibition root growth in A. cepa at 6 different doses. The TAs was increased in a dose-dependent manner too, while mitotic index was decreased at the same doses. Evaluation of mitotic phases revealed mitodepressive effect of AG on A. cepa roots. Conclusion: this work highlights cellular and mitochondrial adverse effects of Atractylis gummifera extracts. A purified fraction that likely corresponds to ATR derivatives induces MPTP opening leading to swelling of mitochondria and its dysfunction. Allium cepa test provides the evidence for A. gummifera genotoxicity and cytotoxicity.

Cytotoxic activity of distinct families of phosphonic acid derivatives - A chemocentric approach to assess their molecular action.

Phosphorus containing small molecules (particularly α-aminophosphonates, α-hydroxyphosphonates and bisphosphonates) represent a unique chemical space among the biologically active compounds. We selected 35 diverse compounds that showed remarkable cytotoxicity effects on various cancer cell lines. However, the exact mechanism of action often requires further investigations, in vitro or in silico target identification even though many target-based activity data were gathered for the above cluster of compounds.

Effect of nitrogen oxides and sulfur oxides to triphenyl phosphate degradation and cytotoxicity on surface of different transition metal salts.

Nitrogen oxides and sulfur oxides, as the dominant toxic gases in the atmosphere, can induce severe human health problems under the composite pollutant conditions. Currently the effect of nitrogen or sulfur oxides in atmospheric environment to the degradation and cytotoxicity of triphenyl phosphate (TPhP) on atmospheric particle surfaces still remain poorly understood. Hence, laboratory simulation methods were used in this study to investigate the effect and related mechanism. First, particle samples were prepared with the TPhP coated on MnSO4, CuSO4, FeSO4 and Fe2(SO4)3 surface. The results showed that, when nitrogen or sulfur oxides were present, more significant TPhP degradation on all samples can be observed under both light and dark conditions. The results proved nitrogen oxides and sulfur oxides were the vital influence factors to the degradation of TPhP, which mainly promoted the OH generation in the polluted atmosphere. The mechanism study indicated that diphenyl hydrogen phosphate (DPhP) and OH-DPhP were two main stable degradation products. These degradation products originated from the phenoxy bond cleavage and hydroxylation of TPhP caused by hydroxyl radicals. In addition, no TPhP related organosulfates (OSs) or organic nitrates (ON) formation were observed. Regarding the cytotoxicity, all the particles can induce more significant cellular injury and apoptosis of A549 cells, which may be relevant to the adsorbed nitrogen oxides or sulfur oxides on particles surfaces. The superfluous reactive oxygen species (ROS) generation was the possible reason of cytotoxicity. This research can supply a comprehensive understanding of the promoting effect of nitrogen and sulfur oxides to TPhP degradation and the composite cytotoxicity of atmospheric particles.

Unveiling the agonistic properties of Preyssler-type Polyoxotungstates on purinergic P2 receptors.

The Preyssler-type polyoxotungstate ({P5W30}) belongs to the family of polyanionic metal-oxides formed by group V and VI metal ions, such as V, Mo and W, commonly known as polyoxometalates (POMs). POMs have demonstrated inhibitory effect on a significant number of ATP-binding proteins in vitro. Purinergic P2 receptors, widely expressed in eukaryotic cells, contain extracellularly oriented ATP-binding sites and play many biological roles with health implications. In this work, we use the immortalized mouse hippocampal neuronal HT-22 cells in culture to study the effects of {P5W30} on the cytosolic Ca2+ concentration. Changes in cytosolic Ca2+ concentration were monitored using fluorescence microscopy of HT-22 cells loaded with the fluorescent Ca2+ indicator Fluo3. 31P-Nuclear magnetic resonance measurements of {P5W30} indicate its stability in the medium used for cytosolic Ca2+ measurements for over 30 min. The findings reveal that addition of {P5W30} to the extracellular medium induces a sustained increase of the cytosolic Ca2+ concentration within minutes. This Ca2+ increase is triggered by extracellular Ca2+ entry into the cells and is dose-dependent, with a half-of-effect concentration of 0.25 ± 0.05 µM {P5W30}. In addition, after the {P5W30}-induced cytosolic Ca2+ increase, the transient Ca2+ peak induced by extracellular ATP is reduced up to 100% with an apparent half-of-effect concentration of 0.15 ± 0.05 µM {P5W30}. Activation of metabotropic purinergic P2 receptors affords about 80% contribution to the increase of Fluo3 fluorescence elicited by {P5W30} in HT-22 cells, whereas ionotropic receptors contribute, at most, with 20%. These results suggest that {P5W30} could serve as a novel agonist of purinergic P2 receptors.

Synthesis and photodynamic activity of new 5-[(E)-2-(3-alkoxy-1-phenyl-1H-pyrazol-4-yl)ethenyl]-2-phenyl-3H-indoles.

A series of new indole-pyrazole hybrids 8a-m were synthesized through the palladium-catalyzed ligandless Heck coupling reaction from easily accessible unsubstituted, methoxy- or fluoro-substituted 4-ethenyl-1H-pyrazoles and 5-bromo-3H-indoles. These compounds exerted cytotoxicity to melanoma G361 cells when irradiated with blue light (414 nm) and no cytotoxicity in the dark at concentrations up to 10 µM, prompting us to explore their photodynamic effects. The photodynamic properties of the example compound 8d were further investigated in breast cancer MCF-7 cells. Evaluation revealed comparable anticancer activities of 8d in both breast and melanoma cancer cell lines within the submicromolar range. The treatment induced a massive generation of reactive oxygen species, leading to different types of cell death depending on the compound concentration and the irradiation intensity.

SARS-CoV-2 BA.4/5 infection triggers more cross-reactive FcγRIIIa signaling and neutralization than BA.1, in the context of hybrid immunity.

SARS-CoV-2 variants of concern (VOCs) differentially trigger neutralizing and antibody-dependent cellular cytotoxic (ADCC) antibodies with variable cross-reactivity. Omicron BA.4/5 was approved for inclusion in bivalent vaccination boosters, and therefore the antigenic profile of antibodies elicited by this variant is critical to understand. Here, we investigate the ability of BA.4/5-elicited antibodies following the first documented (primary) infection (n = 13) or breakthrough infection after vaccination (n = 9) to mediate neutralization and FcγRIIIa signaling across multiple SARS-CoV-2 variants including XBB.1.5 and BQ.1. Using a pseudovirus neutralization assay and a FcγRIIIa crosslinking assay to measure ADCC potential, we show that unlike SARS-CoV-2 Omicron BA.1, BA.4/5 infection triggers highly cross-reactive functional antibodies. Cross-reactivity was observed both in the absence of prior vaccination and in breakthrough infections following vaccination. However, BQ.1 and XBB.1.5 neutralization and FcγRIIIa signaling were significantly compromised compared to other VOCs, regardless of prior vaccination status. BA.4/5 triggered FcγRIIIa signaling was significantly more resilient against VOCs (<10-fold decrease in magnitude) compared to neutralization (10- to 100-fold decrease). Overall, this study shows that BA.4/5 triggered antibodies are highly cross-reactive compared to those triggered by other variants. Although this is consistent with enhanced neutralization and FcγRIIIa signaling breadth of BA.4/5 vaccine boosters, the reduced activity against XBB.1.5 supports the need to update vaccines with XBB sublineage immunogens to provide adequate coverage of these highly antibody evasive variants. IMPORTANCE: The continued evolution of SARS-CoV-2 has resulted in a number of variants of concern. Of these, the Omicron sublineage is the most immune evasive. Within Omicron, the BA.4/5 sublineage drove the fifth wave of infection in South Africa prior to becoming the dominant variant globally. As a result this spike sequence was approved as part of a bivalent vaccine booster, and rolled out worldwide. We aimed to understand the cross-reactivity of neutralizing and Fc mediated cytotoxic functions elicited by BA.4/5 infection following infection or breakthrough infection. We find that, in contrast to BA.1 which triggered fairly strain-specific antibodies, BA.4/5 triggered antibodies that are highly cross-reactive for neutralization and antibody-dependent cellular cytotoxicity potential. Despite this cross-reactivity, these antibodies are compromised against highly resistant variants such as XBB.1.5 and BQ.1. This suggests that next-generation vaccines will require XBB sublineage immunogens in order to protect against these evasive variants.

Thiourea-functionalized aminoglutethimide derivatives as anti-leishmanial agents.

Aim: We aim to develop new anti-leishmanial agents against Leishmania major and Leishmania tropica. Materials & methods: A total of 23 thiourea derivatives of (±)-aminoglutethimide were synthesized and evaluated for in vitro activity against promastigotes of L. major and L. tropica. Results & conclusion: The N-benzoyl analogue 7p was found potent (IC50 = 12.7 µM) against L. major and non toxic to normal cells. The docking studies, indicates that these inhibitors may target folate and glycolytic pathways of the parasite. The N-hexyl compound 7v was found strongly active against both species, and lacked cytotoxicity against normal cells, whereas compound 7r, with a 3,5-bis-(tri-fluoro-methyl)phenyl unit, was active against Leishmania, but was cytotoxic in nature. Compound 7v was thus identified as a hit for further studies.

[Box: see text].

Design, Synthesis of 3-(Aryl)-1-(2-p-tolylthiazol-4-yl)prop-2-en-1-ones as Alpha(α)-Amylase Inhibitors.

α-Amylase inhibition is vital in controlling diabetic complications. Herein, we have synthesized a hybrid scaffold based on thiazole-chalcone to access α-amylase inhbition. The proposed structures were verified with spectroscopic techniques (UV-vis, FT-IR, 1H-, 13C-NMR, and elemental analysis). The synthesized compounds were evaluated for their α-amylase and antioxidant potential. In vitro hemolytic assay was performed to test biocompatibility of all compounds. Among tested compounds, 4c (IC50= 3.8 µM), 4g (IC50= 14.5 µM), and 4f (IC50= 17.1 µM) were found excellent α-amylase inhibitors. However, none of the tested compounds exhibited significant antioxidant activity. All compounds showed less lysis than Triton X-100, but compounds 4f and 4h had the least lysis at all tested concentrations and were found to be safe for human erythrocytes. Molecular docking study was performed to evaluate the binding interactions of ligands with human pancreatic α-amylase (HPA). The binding score -8.09 to -8.507 kcal/mol revealed strong binding interactions in the ligand-protein complex. The docking results supplemented the observed α-amylase inhibition and hence augment the scaffold to serve as leads for the antidiabetic drug development.

Five pimarane diterpenoids from Kaempferia champasakensis and their cytotoxic activities.

A phytochemical investigation of Kaempferia champasakensis rhizomes led to the isolation of five new pimarane diterpenes, kaempferiols E-I (1-5). The structures of 1-5 were elucidated by extensive spectroscopic techniques, including HR-ESI-MS, UV, IR, and 1D and 2D NMR. The absolute configurations of 1-3 were determined by the modified Mosher method, and those of 4 and 5 were established by ECD calculations. Further cytotoxic assay for all isolated compounds against three human cancer cell lines, lung cancer (A549), cervical cancer (HeLa), and breast cancer (MCF-7) indicated that 5 showed moderate cytotoxic activities against the three tested cell lines, with IC50 values of 44.78, 25.97, and 41.39 Mµ for A549, HeLa, and MCF-7 cell lines, respectively.

Surface and composition effects on the biphasic cytotoxicity of nanocomposites synthesized using leaf extracts.

The Malus sylvestris L. (LE1), Pinus sylvestris L. (LE2), and Sorbus aucuparia L. (LE3) leaves` extracts were used for the synthesis of silver (Ag) nanocomposites containing different amounts of silver chloride (AgCl), silver metal (Agmet), and silver phosphate (Ag3PO4). These nanocomposites were capped with the organic functional groups in the leaf extract. Notably, the nanocomposites caused biphasic cytotoxic response on cells; first attributed to the inhibition of cell growth and second to cell death. The nanocomposites were biocompatible with normal embryonic kidney (HEK293) cells in the cytotoxic range for cancer cells. LE2Ag1 [25(±1) °C synthesis] nanocomposites exhibited the highest cytotoxicity towards HeLa (lethal concentration- LC50 value of 11.4 µg mL-1) and A549 (LC50 value of 14.7 µg mL-1) after 24-h incubation and its efficiency was shown also for the more resistant MCF-7 and MDA-MB-231, however, their respective LC50 values were larger. For the HeLa cell line, this designed LE2Ag1 nanocomposite exhibited an LC50 value similar to the effective concentration (EC50) value of Cisplatin and about 3 times larger than Doxorubicin. LE2Ag1 nanocomposite contained Ag3PO4 in the composite and P on the surface, higher AgCl content, smaller crystallite size of all nanoparticle phases, and carbon-rich oxygen-deficient surface compared to all other nanocomposites.

In-vitro hepatotoxic activity of mitragynine and paynantheine isolated from the leaves of Mitragyna speciosa Korth. (Kratom).

Mitragynine, a primary alkaloid found in kratom leaves has been reported to have a broad range of pharmacological and toxicological properties while its congener, paynatheine has comparatively less information available on these aspects. Mitragynine and its congener, paynantheine, were isolated from the ethanol kratom leaves extract using gravity column chromatography techniques. Our study evaluated the cytotoxicity potential of mitragynine and paynantheine on normal human liver cell line, HL-7702, and human hepatoma cell line, HepG2. Mitragynine exhibited a moderate inhibitory effect on the HepG2 cell line with IC50 value of 42.11 ± 1.31 µM in comparison with vinblastine (IC50: 15.45 ± 0.72 µM) while it showed non-cytotoxic properties towards the HL-7702 cell line with concentrations ranging below 200 µM. In contrast, paynantheine exhibited weak cytotoxic properties towards HepG2 and HL-7702 cell lines. Further comprehensive evaluations of both compounds are needed to establish more details on the cytotoxicity potential of kratom alkaloids.

Mancozeb induces cytogenotoxicity in meristematic cells of Allium cepa L.

Mancozeb is a fungicide of the dithiocarbamate functional group, and it is widely used in agriculture to control various fungal diseases. Thus, studies detailing its toxicological characteristics are necessary, as the population may be exposed through the consumption of food or water contaminated with mancozeb. The aim of this study was to evaluate the cytotoxic, genotoxic, and mutagenic potentials of this dithiocarbamate using the Allium cepa L. test system as well as its cytotoxicity in erythrocytes of female rats (Rattus norvegicus). The meristematic roots of A. cepa bulbs were exposed to various concentrations of mancozeb (62.5, 125, 250, and 500 mg/L) for 24, 48, and 72 h to determine cytotoxicity by evaluating the mitotic index (MI), chromosomal aberrations (CA), and nuclear anomalies (NA) for genotoxicity analysis and micronuclei (MN) for mutagenicity analysis. Distilled water and copper sulfate (0.0006 mg/L) were used as the negative control (NC) and positive control (PC), respectively. The MI and the sum of CA and NA of all the mancozeb concentrations showed a significant difference (p ≤ 0.05) in relation to the NC, indicating possible cytotoxicity and genotoxicity induced by mancozeb. Additionally, MN significantly increased with mancozeb concentration from 250 mg/L to 500 mg/L in 24 h when compared to NC. In another study model, mancozeb showed to be cytolytic at concentrations starting from 125 mg/L. Therefore, these results indicate that mancozeb causes cytogenetic alterations and mutagenicity at lower concentrations than those used in agriculture, which emphasizes the need for more care when managing this fungicide.

Synthesis of curcumin derivatives targeting androgen receptor for castration-resistant prostate cancer therapy.

In this work, a series of curcumin derivatives (1a-1h, 2a-2g, and 3a-3c) were synthesized for the suppression of castration-resistant prostate cancer cells. All synthesized compounds were characterized by 1H NMR, 13C NMR, HRMS, and melting point. The in vitro cytotoxicity study shows that compounds 1a, 1e, 1f, 1h, 2g, 3a, and 3c display similar or enhanced cytotoxicity against 22Rv1 and C4-2 cells as compared to ASC-J9, other synthesized compounds display reduced cytotoxicity against 22Rv1 and C4-2 cells as compared to ASC-J9. Molecular docking simulation was performed to study the binding affinity and probable binding modes of the synthesized compounds with androgen receptor. The results show that all synthesized compounds exhibit higher cdocker interaction energies as compared to ASC-J9. Compounds 1h, 2g, and 3c not only show strong cytotoxicity against 22Rv1 and C4-2 cells but also exhibit high binding affinity with androgen receptor. In androgen receptor suppression study, compounds 1f and 2g show similar androgen receptor suppression effect as compared to ASC-J9 on C4-2 cells, compound 3c displays significantly enhanced AR suppression effect as compared to ASC-J9, 1f and 2g. Compounds 1a, 1e, 1f, 1h, 2g, 3a and 3c prepared in this work have significant potential for castration-resistant prostate cancer therapy.

Construction and antibacterial activities of walnut green husk polysaccharide based silver nanoparticles (AgNPs).

In this paper, the size-controllable nano­silver particles (AgNPs) were synthesized from walnut green husk polysaccharide, and its cytotoxicity and antibacterial activity were evaluated. Firstly, acidic polysaccharide WGHP2 was extracted from walnut green husk, and then the silver ion in AgNO3 was reduced in WGHP2 aqueous solution using NaBH4, so as to synthesize the nano­silver composite. The nano­silver composite was characterized by transmission electron microscope, Fourier infrared spectroscopy, ultraviolet-visible spectrometer, scanning electron microscope, inductively coupled plasma mass spectrometry and X-ray photoelectron spectroscopy. The results show that AgNPs stabilized by WGHP2 are mainly regular spheres with an average particle size distribution of 15.04-19.23 nm. The particle size distribution and morphology of AgNPs changed with the concentration of silver precursor, which is related to the dispersion of silver precursor in polysaccharide aqueous solution and the formation of AgO coordination bond between silver precursor and polysaccharide molecules. These coordination bonds changed the ability of nanoparticles to produce and release Ag+, and thus regulated their antibacterial activity and cytotoxicity, as evidenced by the experimental result of the cytotoxicity of the nano­silver particle against PC12 cells and the bacteriostatic effect on E.coli and S.aureus. Conclusively, WGHP2-Ag has good stability, antibacterial activity and low cytotoxicity.

In silico Screening and in vitro Cytotoxicity Study of Achyranthes aspera Phytochemicals Against Oral Cancer: A Possible Step towards the Development of Anti-cancer Agents.

BACKGROUND: Oral cancer poses a significant threat to public health worldwide. In addition, because many chemotherapy treatments have negative side effects, natural herbs may be beneficial for oral cancer therapy. Achyranthes aspera (AA), a potential medicinal herb, exerts various pharmacological and biochemical activities. OBJECTIVE: The present study aimed to predict the anti-oral cancer potential of AA using in silico tools and cell death by in vitro testing. METHODS: A total of fourteen bioactive constituents from AA herb were selected using phytochemical databases. The toxicity of AA herb extract was analysed through MTT assay against oral carcinoma A253 cell line. The binding activities of the phytocomponents against serine/ threonine-specific protein kinases isoforms, namely Akt1 (PDB ID: 3qkk) and Akt2 (PDB ID: 2jdo) proteins, were analysed using Discovery Studio 2021 and PyRx docking software. RESULTS: Cell viability data revealed that AA extract decreased the viability and reduced the number of live cells of the oral carcinoma A253 cell line in a dose-dependent manner. The halfmaximal concentration (IC50) value of AA was assessed as 204.74 µg/ml. Based on binding affinity, saponin C (-CDOCKER energy = -77.9862), oleanolic acid (-CDOCKER energy = - 49.4349), spinasterol (-CDOCKER energy = -38.1246), 36,47-dihydroxyhenpentacontan-4-one (-CDOCKER energy = -32.4386), and 20-hydroxyecdysone (-CDOCKER energy = -31.9138) were identified as the best compounds against Akt1, while, compounds saponin C (-CDOCKER energy = -134.412), oleanolic acid (-CDOCKER energy = -90.0846), spinasterol (-CDOCKER energy = -78.3213), 20-hydroxyecdysone (-CDOCKER energy = -80.1049), and ecdysone (- CDOCKER energy = -73.3885) were identified as Akt2 inhibitors. These top compounds fulfilled drug score values, pharmacokinetic and physicochemical characteristics, and druglikeness parameters. CONCLUSION: The present findings reveal that the lead phytomolecules of AA could be effective and developed as a prospective drug against oral cancer.

Potent and Selective Oxidatively Labile Ether-Based Prodrugs through Late-Stage Boronate Incorporation.

This manuscript describes a new strategy for prodrug synthesis in which a relatively inert ether group is introduced at an early stage in a synthetic sequence and functionalized in the final step to introduce a prodrug-activating group through a chemoselective  process. Boryl allyloxy (BAO) ether groups are synthesized through several metal-mediated processes to form entities that are readily cleaved under oxidative conditions commonly found in cancer cells. The high cleavage propensity of the BAO group allows for ether cleavage, making these compounds substantially more hydrolytically stable in comparison to acyl-linked prodrugs while retaining the ability to release alcohols. We report the preparation of prodrug analogues of the natural products camptothecin and pederin from acetal precursors that serve as protecting groups in their synthetic sequences. The BAO acetal groups cleave in the presence of hydrogen peroxide to release the cytotoxic agents. The pederin-based prodrug shows dramatically greater cytotoxicity than negative controls and outstanding selectivity and potency toward cancer cell lines in comparison to non-cancerous cell lines. This late-stage functionalization approach to prodrug synthesis should be applicable to numerous systems that can be accessed through chemoselective processes.

An extended flow cytometry evaluation of ex vivo expanded NK cells using K562.Clone1, a feeder cell line manufactured in Brazil.

BACKGROUND: Natural Killer (NK) cells play a crucial role in the immune system's response against cancer. However, the challenge of obtaining the required quantity of NK cells for effective therapeutic response necessitates the development of strategies for their ex vivo expansion. OBJECTIVE: This study aimed to develop a novel feeder cell line, K562.Clone1, capable of promoting the ex vivo expansion of NK cells while preserving their cytotoxic potential. STUDY DESIGN: The K562 leukemic cell line was transduced with mbIL-21 and 4-1BBL proteins to generate K562.Clone1 cells. NK cells were then co-cultured with these feeder cells, and their expansion rate was monitored over 14 days. The cytotoxic potential of the expanded NK cells was evaluated against acute myeloid leukemia blasts and tumor cell lines of leukemia and glial origin. Statistical analysis was performed to determine the significance of the results. RESULTS: The K562.Clone1 co-cultured with peripheral NK showed a significant increase in cell count, with an approximately 94-fold expansion over 14 days. Expanded NK cells demonstrated cytotoxicity against the tested tumor cell lines, indicating the preservation of their cytotoxic characteristics. Additionally, the CD56, CD16, inhibitory KIRs, and activation receptors were conserved and present in a well-balanced manner. CONCLUSION: The study successfully developed a feeder cell line, K562.Clone1, that effectively promotes the expansion of NK cells ex vivo while maintaining their cytotoxic potential. This development could significantly contribute to the advancement of NK cell therapy, especially in Brazil.

Synthesis and characterization of novel carboxymethyl inulin derivatives bearing cationic Schiff bases with antioxidant potential.

This study aimed to enhance the antioxidant activity of carboxymethyl inulin (CMI) by chemical modification. Therefore, a series of cationic Schiff bases bearing heteroatoms were synthesized and incorporated into CMI via ion exchange reactions, ultimately preparing 10 novel CMI derivatives (CMID). Their structures were confirmed by Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy. The radical scavenging activities and reducing power of inulin, CMI, and CMID were studied. The results revealed a significant enhancement in antioxidant activity upon the introduction of cationic Schiff bases into CMI. Compared to commercially available antioxidant Vc, CMID demonstrated a broader range of antioxidant activities across the four antioxidant systems analyzed in this research. In particular, CMID containing quinoline (6QSCMI) exhibited the strongest hydroxyl radical scavenging activity, with a scavenging rate of 93.60 % at 1.6 mg mL-1. The CMID bearing imidazole (2MSCMI) was able to scavenge 100 % of the DPPH radical at 1.60 mg mL-1. Furthermore, cytotoxicity experiments showed that the products had good biocompatibility. These results are helpful for evaluating the feasibility of exploiting these products in the food, biomedical, and cosmetics industries.

Tripeptide linked dispiro cyclotriphosphazene conjugates: Synthesis, molecular docking analysis of compounds binding within cancer cell line receptors and in vitro cytotoxic and genotoxic activities.

The novel dioxybiphenyl bridged-cyclotriphosphazenes (DPP) bearing tripeptide were synthesized and investigated for their molecular docking analysis, visualizing their binding profiles within various cancer cell line receptors and in vitro cytotoxic and genotoxic properties. The dipeptide compound (Tyr-Phe) was treated with various amino acids to obtain the tripeptide compounds (Tyr-Phe-Gly, Tyr-Phe-Ala, Tyr-Phe-Val, Tyr-Phe-Phe, and Tyr-Phe-Leu). These synthesized tripeptides were subsequently treated with DPP to obtain novel phosphazene compounds bearing tripeptide structures. As a result, the synthesis of target molecules with phosphazene compound in the center and biphenyl and tripeptide groups in the side arms was obtained for the first time in this study. Examining the cytotoxic studies in vitro of our newly synthesized compounds demonstrated the anticancer properties against four selected human cancer cell lines, including breast (MCF-7), ovarian (A2780), prostate (PC-3), and colon (Caco-2) cancer cells. The Comet Assay analysis determined that the cell death mechanism of most of the compounds with cytotoxic activity stemmed from the DNA damage mechanism. Among the compounds, the DPP-Tyr-Phe-Phe compound seems to have the best anticancer activity against the subjected cell lines (Except for A2780) with IC50 values equal to 20.18, 72.14, 12.21, and 5.17 µM against breast, ovarian, prostate, and colon cancer cell lines, respectively. For this reason, the molecular docking analysis was conducted for the DTPP compound to visualize its binding geometry and profile within the target enzyme's binding site associated with the specific cancer cell line. The analysis revealed that the DTPP derivative exhibited an optimal binding conformation and characteristics within the target enzyme's binding site, aligning well with the experimental data. Based on the data, these compounds are believed to be strong candidate molecules for both pharmaceutical and clinical applications.

Dehydroabietylamine-substituted trifluorobenzene sulfonamide rhodamine B hybrids as anticancer agents overcoming drug resistance.

Attachment of a conjugate assembled from a novel fluorinated carbonic anhydrase inhibitor and rhodamine B onto dehydroabietylamine (DHA) or cyclododecylamine led to first-in-class conjugates of good cytotoxicity; thereby IC50 values (from SRB assays; employed tumor cell lines A2780, A2780Cis, A549, HT29, MCF7, and non-malignant human fibroblasts CCD18Co) between 0.2 and 0.7 µM were found. Both conjugates showed similar cytotoxic activity but the dehydroabietylamine derived conjugate outperformed its cyclododecyl analog in terms of tumor cell/non-tumor cell selectivity. Both conjugates accumulate intracellular, and the DHA conjugate was able to overcome drug resistance which is effective independent of the expression status of carbonic anhydrase IX.