Human Cancer Cell Lines Research Articles

Tailoring carrier-free nanoparticles based on natural small molecule assembly for synergistic anti-tumor efficacy

Interfacial modular assemblies of versatile polyphenols have attracted widespread interest in surface and materials engineering. In this study, natural polyphenol (tannic acid, TA) and nobiletin (NOB) can directly form binary carrier-free spherical nanoparticles (NT NPs) through synergistically driven by a variety of interactions (such as hydrogen bonding, oxidative reactions, etc.). The synthesis involves polyphenolic deposition on hydrophobic NOB nanoaggregates, followed by in situ oxidative self-polymerization. Interestingly, the assembled NT NPs exhibit controllable and dynamic changes in particle size during the initial stage. Ultimately, uniform and spherical NT NPs appear stable, with high loading capability, enabling incorporated NOB to preserve their function. Furthermore, in vitro evaluations demonstrate that the rational combination of polyphenol module and NOB can induce apoptosis and inhibit tumor metastasis for both lung cancer H1299 and human fibrosarcoma HT1080 cell lines. Notably, the optimized NT48 NPs were then verified in vivo experiments to achieve a promising synergistic anti-tumor efficacy. These findings not only provide new opportunities for the streamlined and sensible engineering of future polyphenol-based biomaterials, but also open up new prospects for the design of small-molecule nature phytochemicals.

In Vitro Cytotoxicity and Mechanistic Investigation of Quinazolin-4(1H)-One Linked Coumarin as a Potent Anticancer Agent.

Quinazolinone-coumarin conjugates synthesized through Late-Stage Functionalization approach are evaluated for their invitro biological activity for 60 human cancer cell lines representing nine different cancer types. Among the synthesized compounds, eight displayed significant growth inhibitory activity across a spectrum of cancer types, with compound 23 demonstrating particularly notable cytotoxicity. Further investigation involved a five-dose assay of compound 23 against NCI-60 cancer cell lines, revealing its efficacy at different concentrations. Additionally, binding studies elucidated its interaction with Human Serum Albumin (HSA) and DNA. The results indicated a strong binding affinity of 23 with HSA, evidenced by a high binding constant (2.26 × 105 M-1). Moreover, its interaction with DNA occurred via intercalation, specifically between the base pairs of DNA strands, with a binding constant of 5.51 × 104 M-1. This suggests that compound 23 has the ability to bind to both DNA and transport proteins, making it a promising pharmacophore with potential therapeutic applications.

HERC5: a comprehensive in silico analysis of its diagnostic, prognostic, and therapeutic potential in cancer.

HERC5, a vital protein in the HERC family, plays crucial roles in immune response, cancer progression, and antiviral defense. This bioinformatic study comprehensively assessed HERC5's significance across various malignancies by analyzing its gene expression, immune and molecular subtype expressions, target proteins, biological functions, and prognostic and diagnostic values in pan-cancer. We further examined its correlation with clinical features, co-expressed and differentially expressed genes, and prognosis in clinical subgroups, focusing on endometrial cancer (UCEC). Our findings showed that HERC5 RNA is expressed at low levels in most cancers and significantly differs across immune and molecular subtypes. HERC5 accurately predicts cancer and correlates with most cancer prognoses. In UCEC, HERC5 was significantly associated with age, hormonal status, clinical stage, treatment status, and metastasis. Elevated HERC5 expression was linked to worse progression-free interval, disease-specific survival, and overall survival in UCEC, particularly in diverse clinical subgroups. Significant differences in HERC5 expression were also observed in various human cancer cell line validations. In summary, HERC5 may be a critical biomarker for pan-cancer prognosis, progression, and diagnosis, as well as a promising new target for cancer therapy.

TRBP2, a Major Component of the RNAi Machinery, Is Subjected to Cell Cycle-Dependent Regulation in Human Cancer Cells of Diverse Tissue Origin.

Transactivation Response Element RNA-binding Protein (TRBP2) is a double-stranded RNA-binding protein widely known for its critical contribution to RNA interference (RNAi), a conserved mechanism of gene-expression regulation mediated through small non-coding RNA moieties (ncRNAs). Nevertheless, TRBP2 has also proved to be involved in other molecular pathways and biological processes, such as cell growth, organism development, spermatogenesis, and stress response. Mutations or aberrant expression of TRBP2 have been previously associated with diverse human pathologies, including Alzheimer's disease, cardiomyopathy, and cancer, with TRBP2 playing an essential role(s) in proliferation, invasion, and metastasis of tumor cells. Hence, the present study aims to investigate, via employment of advanced flow cytometry, immunofluorescence, cell transgenesis and bioinformatics technologies, new, still elusive, functions and properties of TRBP2, particularly regarding its cell cycle-specific control during cancer cell division. We have identified a novel, mitosis-dependent regulation of TRBP2 protein expression, as clearly evidenced by the lack of its immunofluorescence-facilitated detection during mitotic phases, in several human cancer cell lines of different tissue origin. Notably, the obtained TRBP2-downregulation patterns seem to derive from molecular mechanisms that act independently of oncogenic activities (e.g., malignancy grade), metastatic capacities (e.g., low versus high), and mutational signatures (e.g., p53-/- or p53ΔΥ126) of cancer cells. Taken together, we herein propose that TRBP2 serves as a novel cell cycle-dependent regulator, likely exerting mitosis-suppression functions, and, thus, its mitosis-specific downregulation can hold strong promise to be exploited for the efficient and successful prognosis, diagnosis, and (radio-/chemo-)therapy of diverse human malignancies, in the clinic.

Phosphine-Catalyzed [4 + 1] Annulation of β'-Acetoxy Allenoate with α-Alkylidene Succinimides: Access to Functionalized Spirosuccinimide Derivatives.

A phosphine-catalyzed [4 + 1] annulation of β'-acetoxy allenoate with α-alkylidene succinimides is described. This method demonstrates the nucleophilic dialkylation and cyclization of α-alkylidene succinimides, resulting in the formation of functionalized spirosuccinimide derivatives. The reaction exhibits a wide substrate scope and yields ranging from moderate to excellent under the optimized conditions. In addition, the biological evaluation indicates that the cycloadduct 3u presents satisfied inhibitory activities for three human cancer cell lines (HCT116, A549, and HepG2).

Environment-friendly Synthesis of AgNPs from Fimbristylis miliacea Flower Extract: Characterization and its Applications as an Antioxidant Activity, Anticancerous Activity and in the Reduction of 4-Nitrophenol

Background: Silver metal is useful in a variety of fields. Different silver salts exhibit good application in the organic transformation. The use of a green methodology in AgNPs preparation has gained interest of young researchers. Plant systems are employed in the green approach of preparing AgNPs, serving as both a stabilizing and reducing agent. Silver nanoparticles (AgNPs) made from silver salts exhibit a variety of biological activities and may be useful in organic transformation. Method: AgNPs were synthesized with the use of flower extract from Fimbristylis miliacea, which acts as a stabilizing and reducing agent. Result: Fimbristylis miliacea flower extract is used as a reducing and stabilising agent for preparation of AgNPs. These synthesised AgNPs were characterised by using FTIR, XRD, FESEM/ EDS, HR-TEM, TGA, and ICP-AES. Fimbristylis milliciea flower extract was subjected to FTIR and HR-LCMS analysis in order to identify the phytoconstituents that are responsible for the reduction of AgNO3. The HR-TEM shows particle size between 8.98434+0.69669nm and 19.07464+1.4384nm. The size of AgNPs determined by using HR-TEM shows good agreement with XRD particle size. The synthesized AgNPs show excellent antioxidant properties with IC50=56.45 μg/mL. The present study confers significant cytotoxic activity against MDA-MB-231 human breast cancer cell line culture (IC50= 61.97 μg/ml). The AgNPs show a faster reduction of 4-nitrophenol. Conclusion: In conclusion, we have prepared AgNPs by using Fimbristylis miliacea flower extract. The study further concludes that green synthesis of AgNPs has many advantages as compared to chemical methods, such as cost-effectiveness, rapid, and environment-friendly methods. The results indicated that the biosynthesized AgNPs have significant cytotoxic activity against the MDA-MB-231 breast cancer cell line. Further, it indicates that biosynthesized AgNPs can be a potential alternative agent for human breast cancer therapy. The cytotoxic potential can be used for treatments and provides a new method to develop molecules for cancer therapy. The catalytic activity of AgNPs was examined by using the reduction of 4-nitrophenol. It shows that the reduction of 4-nitrophenol in 6 minutes is confirmed by using 1H NMR analysis.

Evaluation of Antioxidant and Breast Cancer Cytotoxicity of Beta vulgaris and Daucus carota Methanol Extracts

Breast cancer is the world's most frequent malignancy among women. Many dietary antioxidants have been shown to help prevent oxidative stress, which has been linked to a variety of diseases, including cancer. Many chronic diseases, such as cancer, can be avoided by eating fruits and vegetables on a regular and balanced basis. The current study's goal is to assess the antioxidant and cytotoxic capabilities of methanolic extracts of Beta vulgaris and Daucus carota against MCF-7 human breast cancer cell lines. Therefore, the aim of the present study was to determine the phytochemical components, antioxidant capacity, total phenolic & flavonoid contents in the methanolic extracts of Beta vulgaris and Daucus carota. Further, MTT assay against breast cancer cell line (MCF-7) was performed for the evaluation of cytotoxic activity. The majority of secondary metabolites were found in both the aqueous and methanolic extracts of Beta vulgaris and Daucus carota. Beta vulgaris and Daucus carota have different total phenolic and flavonoid contents. TLC results showed many spots having different Rf values. Moreover, we observe comparable cytotoxic activity in both the extracts against MCF-7 cell lines. Our results reveal that the methanolic extracts of Beta vulgaris and Daucus carota has effective phytochemical constituents, antioxidant and anticancer activity. The total phenolic and flavonoid contents vary between Beta vulgaris and Daucus carota. Further studies are needed to evaluate the chemopreventive potentials of the Beta vulgaris and Daucus carota extract when used alone or in combination with doxorubicin to mitigate the toxic side-effects of the latter.

Synergistic Combination of Quercetin and Mafosfamide in Treatment of Bladder Cancer Cells.

Bladder cancer, which has a rising incidence, is the 10th most common cancer. The transitional cell carcinoma histotype is aggressive and often current therapies are ineffective. We investigated the anti-proliferative effect of quercetin, a natural flavonoid, in combination with the alkylating agent mafosfamide (MFA) on two human bladder cancer cell lines, namely RT112 and J82, representing the progression from low-grade to high-grade tumors, respectively. In both cell types, the combined treatment led to a synergic reduction in cell viability confirmed by a combination index of less than one, though different biological responses were noted. In J82 cells, MFA alone and, to a lesser extent, with quercetin caused cell cycle arrest in the G2/M phase, but only the combined treatment triggered apoptotic cell death. In contrast, in RT112 cells, quercetin induced autophagy, evidenced by the autophagosome formation and the increase in LC-3 lipidation. Interestingly, the synergistic effect was observed only when cells were pre-treated with MFA for 24 h before adding quercetin, not in the reverse order. This suggests that quercetin may help overcome MFA resistance to apoptosis. Although further studies are needed, investigating the combined effects of quercetin and MFA could help elucidate the mechanisms of drug resistance in bladder cancer treatment.

Synthesis of (-)-Cannabidiol (CBD), (-)-Δ9- and (-)-Δ8-Tetrahydrocannabinols, Encapsulation of CBD with Nanoparticles for Controlled Delivery and Biological Evaluation.

Cannabidiol (CBD) is garnering increasing interest due to its significant biological activity. This natural compound is one of the major cannabinoids in Cannabis sativa L. In this work, we describe the encapsulation of CBD in solid and hollow pH-sensitive poly(4-vinylpyridine) (solid@p4VP and hollow@p4VP) nanoparticles, and temperature-sensitive poly(N-isopropylacrylamide) (solid@pNIPAM and hollow@pNIPAM) nanoparticles for transport and release CBD in a controlled manner. The CBD loading into these smart polymeric systems was effective and their release profiles, solubility and resistance to stomach and intestinal conditions were evaluated, showing satisfactory properties and improved bioavailability with respect to free CBD. Finally, the A549 human lung cancer cell line was used as lung adenocarcinoma epithelial cellular model to carry out preliminary assays of the in vitro activity of the vehiculized CBD. For all these studies, synthetic CBD was employed, for which a new efficient and scalable synthesis of cannabinoids has been developed.

Design, synthesis, and in vitro and in vivo biological evaluation of dihydroartemisinin derivatives as potent anti-cancer agents with ferroptosis-inducing and apoptosis-activating properties

Natural products play a pivotal role in drug development, including their direct use as pharmaceuticals and their structural modification, yielding molecules with enhanced therapeutic potential. The discovery of bioactive molecules, lead compounds, and novel drugs is intrinsically linked to the structural optimization of natural products. In this study, forty-one derivatives of dihydroartemisinin (DHA) were synthesized by incorporating fragments with anti-tumour activity via molecular hybridization, and assessed for their anti-proliferative activity against human cancer cell lines (A549, Bel-7402, HCT-116, and SW620) and normal human liver cells (LO2). Most derivatives exhibited superior anti-proliferative activity compared to DHA. Notably, compound A3, featuring a 4-Cl phenyl carbamate moiety, demonstrated significant anti-proliferative activity against HCT-116 cells with an IC50 of 0.31 μM, making it 16-fold more potent than DHA (IC50 = 5.10 μM). The anti-proliferative mechanism did not involve cytotoxicity (SI = 54.13), indicating its superior safety profile compared to DHA (SI = 1.65).Further mechanistic studies revealed that compound A3 inhibits HCT-116 cell proliferation by modulating the expression of PI3K/AKT/mTOR and STAT3 proteins. STAT3 downregulation represses the expression of the critical ferroptosis protein glutathione peroxidase 4 (GPX4), aggravating the accumulation of reactive oxygen species (ROS) and depletion of glutathione (GSH). This redox imbalance triggers and accelerates ferroptosis. Additionally, A3 also induces apoptosis by damaging mitochondria and influencing MAPK signaling. Compound A3 arrested cells in the G2/M phase by regulating p53 expression. In an HCT-116 xenograft mouse model, compound A3 exhibited significant anti-cancer efficacy, with a tumor growth inhibition rate of 58.7 %. Therefore, compound A3 thus has the potential to serve as a lead compound for the development of new anti-tumor drugs.

Tumour-intrinsic PDL1 signals regulate the Chk2 DNA damage response in cancer cells and mediate resistance to Chk1 inhibitors

BackgroundAside from the canonical role of PDL1 as a tumour surface-expressed immune checkpoint molecule, tumour-intrinsic PDL1 signals regulate non-canonical immunopathological pathways mediating treatment resistance whose significance, mechanisms, and therapeutic targeting remain incompletely understood. Recent reports implicate tumour-intrinsic PDL1 signals in the DNA damage response (DDR), including promoting homologous recombination DNA damage repair and mRNA stability of DDR proteins, but many mechanistic details remain undefined.MethodsWe genetically depleted PDL1 from transplantable mouse and human cancer cell lines to understand consequences of tumour-intrinsic PDL1 signals in the DNA damage response. We complemented this work with studies of primary human tumours and inducible mouse tumours. We developed novel approaches to show tumour-intrinsic PDL1 signals in specific subcellular locations. We pharmacologically depleted tumour PDL1 in vivo in mouse models with repurposed FDA-approved drugs for proof-of-concept clinical translation studies.ResultsWe show that tumour-intrinsic PDL1 promotes the checkpoint kinase-2 (Chk2)-mediated DNA damage response. Intracellular but not surface-expressed PDL1 controlled Chk2 protein content post-translationally and independently of PD1 by antagonising PIRH2 E3 ligase-mediated Chk2 polyubiquitination and protein degradation. Genetic tumour PDL1 depletion specifically reduced tumour Chk2 content but not ATM, ATR, or Chk1 DDR proteins, enhanced Chk1 inhibitor (Chk1i) synthetic lethality in vitro in diverse human and murine tumour models, and improved Chk1i efficacy in vivo. Pharmacologic tumour PDL1 depletion with cefepime or ceftazidime replicated genetic tumour PDL1 depletion by reducing tumour Chk2, inducing Chk1i synthetic lethality in a tumour PDL1-dependent manner, and reducing in vivo tumour growth when combined with Chk1i.ConclusionsOur data challenge the prevailing surface PDL1 paradigm, elucidate important and previously unappreciated roles for tumour-intrinsic PDL1 in regulating the ATM/Chk2 DNA damage response axis and E3 ligase-mediated protein degradation, suggest tumour PDL1 as a biomarker for Chk1i efficacy, and support the rapid clinical potential of pharmacologic tumour PDL1 depletion to treat selected cancers.

Gold(I) complexes of the type [AuL{κC-2-C6H4P(S)Ph2}] [L = PTA, PPh3, PPh2(C6H4-3-SO3Na) and PPh2(2-py)]: Synthesis, characterisation, crystal structures, and In Vitro and In Vivo anticancer properties

Four new mononuclear gold (I) compounds of the type [AuL{κC-2-C6H4P(S)Ph2}] {L = PTA (1), PPh3 (2), PPh2(C6H4-3-SO3Na) (3), and PPh2(2-py) (4)} were prepared by scission of the dinuclear compound [Au2{μ-2-C6H4P(S)Ph2}2] by L or via a transmetalation reaction using the organotin reagent 2-Me3SnC6H4P(S)Ph2 and a suitable gold halide precursor. The cytotoxic potential of complexes 1–4 was evaluated against four human cancer cell lines of diverse cellular origin: cervical (HeLa), prostate (PC-3), non-small cell lung adenocarcinoma (A549), and fibrosarcoma (HT-1080). The in vitro cytotoxicity results showed that 1 demonstrated exceptional anticancer activity with IC50 values ranging from 0.08 to 3.5 μM. Complex 3, which contains a sulfonated triphenyl phosphine ligand, displayed the weakest anticancer activity with IC50 values ranging from 3.1 to >50 μM. When compared to the standard chemotherapeutic drug cisplatin, 1 displayed approximately 27-fold greater cytotoxic activity against cervical cancer cells and 3.5- and 7.5-fold greater activities against prostate and fibrosarcoma cancer cells, respectively. Additionally, 1 exhibited 3-fold selectivity for cervical cancer cells compared to non-cancerous HEK-293 cells. Mechanistic investigations revealed that 1 induced apoptosis, which was associated with elevated reactive oxygen species (ROS) and inhibition of the intracellular enzyme thioredoxin reductase. Furthermore, 1 exhibited notable antiangiogenic characteristics in an in vivo model using transgenic zebrafish Tg(fli1a:EGFP). In vivo studies using mouse xenograft models showed that complex 1 displayed superior inhibition of tumour growth (82 %) compared to the clinical drug cisplatin (29 %). Overall, these results highlight the potential of gold (I) compounds as novel antitumour agents.

Resveratrol‐Loaded Silver Nanoparticles as an Effective Strategy for Targeted Breast Cancer Therapy

AbstractThe AgNPs‐Rsvl complex was investigated for its anti‐cancer effects on human breast cancer cell lines. The UV–vis spectrophotometer was used to perform synthesized AgNPs‐Rsvl binding analyses. The size and morphology of the AgNPs were determined by field emission gun‐transmission electron microscopy (FEG‐TEM). The surface chemical signatures of AgNPs nanocomposites were assessed using FT‐IR spectroscopy, and the zeta potential (ζ potential) of various AgNPs colloids was measured using the Zetasizer Nano ZS analyzer. Cell proliferation was analyzed using the XTT method and cell apoptosis was analyzed using the AnnexinV‐fluorescein isothiocyanate (FITC)/PI method. The effects of resveratrol were evaluated on human breast cancer cell lines (MDA‐MB‐231 and MCF‐7). As a result of flow cytometry, a decrease in viability was observed in the MDA‐MB‐231 cells, and an increase in early apoptotic, late apoptotic, and necrotic values was observed. Resveratrol arrests the cell cycle in the G0/G1 phase but when used with AgNPs, the cell cycle arrests at the S phase. The combination of resveratrol and AgNPs exhibited a cytotoxic effect on cancer cells, with MDA‐MB‐231 breast cancer cells being the most sensitive to AgNPs‐Rsvl. Resveratrol and AgNPs arrested the cell cycle and increased apoptosis, indicating their potential use in breast cancer treatment.

Probing Host‐Guest Inclusion Complex of DHP with β‐CD in Augmenting Bioavailability to Boost Biochemical Applications Optimized by Physicochemical and Molecular Docking

AbstractThis research aims to develop the inclusion complex of 2, 4‐diamino‐6‐hydroxypyrimidine (DHP) with β‐cyclodextrin (β‐CD) using an inclusion process, and to investigate the effect of inclusion on the photo stability and bioactivity of DHP. The formation of DHP‐β‐CD inclusion complex has been examined by means of physicochemical as well as spectroscopic techniques (1H NMR, FT‐IR, PXRD and SEM) suggesting the successful inclusion of the DHP molecule into the β‐CD cavity. The 1 : 1 stoichiometry of the inclusion complex was validated through Job's plot. β‐CD displayed a fairly strong affinity (Ka =889.67 M−1) for DHP, indicating that the binding process is thermodynamically feasible. A molecular docking study speculated the most preferred orientation of DHP molecule within the binding pocket of β‐CD cavity. The photostability of DHP was found to improve on complexation with β‐CD. In vitro antibacterial activity test demonstrated that the DHP‐β‐CD inclusion complex displayed better activity than pure DHP. DHP‐β‐CD inclusion complex (IC50 =240.04 μM) also exhibited relatively significant in vitro cytotoxic activity than pure DHP towards the human kidney cancer cell line (ACHN). These results reveals that the inclusion of DHP using β‐CD could lead to stabilization of DHP and efficient display of its bioactivity.

Phosphoinositide 3-Kinase Inhibitors from Gladiolus Segetum Ker-Gawl Corms Supported by Network Pharmacology.

Gladiolus segetum Ker-Gawl corms total extract exhibited remarkable in vitro anti-proliferative effects against panel of cancer cell lines; including human colon carcinoma (Caco-2), human breast cancer (MCF7) and hepatocellular carcinoma (HepG2) cell lines with IC50 values of 7.4, 9.1 and 11.2 μg/ml, respectively. The total ethanolic extract of G. segetum Ker-Gawl corms was subjected to untargeted metabolomics profiling using LC-HR-ESI-MS, which revealed the presence of various clusters of phytoconstituents as triterpenes, anthraquinones, flavonoids and phenolic derivatives. Network pharmacology study was performed for all identified compounds, the formed networks identified 73 intersected genes. The diagrammatic illustration of the top pathways revealed that phosphoinositide 3-kinase (PI3 K) gene is the effective dominant gene in the top four KEGG pathways. Upon molecular docking and molecular dynamics investigation, kaempferol-3-O-glucopyranoside was suggested to be key anticancer metabolite. Interestingly, cytotoxic investigation of this compound revealed potential activity against the tested cancer cell lines (Caco-2, MCF7 and HepG2) with IC50 values of 6.2, 8.5 and 9.3 μg/ml, respectively. The present study highlighted the potential of G. segetum Ker-Gawl as a promising source of interesting anticancer scaffolds.

Differential Effects of Punicic Acid on Cytotoxicity and Peroxiredoxin Expression in MCF-7 Breast Cancer and MCF-10A Normal Cells.

The pomegranate fruit has been associated with a variety of human health benefits based on its antioxidant and anti-inflammatory properties. Punicic acid (PA) is an omega-5 long chain polyunsaturated fatty acid that constitutes approximately 65-80% of the oil from pomegranate seeds and has been found to possesses anti-cancer activity in various cancer types. To better understand its cell specificity, we investigated the effects of punicic acid on both the MCF-7 human breast cancer cell line as well as the non-cancerous MCF-10A breast epithelial line. We treated both cell types with different concentrations of punicic acid and measured viable cell density, cytotoxicity and apoptosis, as well as peroxiredoxin (Prdx) antioxidant expression. We found that punicic acid was cytotoxic to both lines, but MCF-10A cells demonstrated higher levels of cytotoxicity and sensitivity to lower concentrations. We further demonstrated that cytotoxicity was associated with apoptosis in both lines. Using real time PCR, we demonstrated induction of all six Prdx mRNAs in MCF-7 cells, ranging from a 1.4-fold increase with 2 μg/ml, to over a 5-fold increase with 10 μg/ml. In stark contrast, MCF-10A cells exhibited considerably higher induction of all six Prdx mRNAs at 10μg/ml, exceeding a 30-fold induction of Prdx1, Prdx2 and Prdx5. Our data are the first to demonstrate differential cytotoxicity and Prdx regulation by punicic acid in these two cell lines. These results may provide important insight into cell-specific mechanisms of punicic acid in breast cancer.

Synthesis, Characterization, and Molecular Docking of Novel Isatin-thiosemicarbazone containing 1,2,3-triazole Derivatives as Potential Anti-cancer Agents

Abstract: To improve the activity of isatin-1,2,3-triazole hybrids as anticancer agents, new derivatives of isatin- thiosemicarbazone-1,2,3-triazoles 9-16 were designed and synthesized via the condensation of isatin-1,2,3- triazole hybrids 1-8 with thiosemicarbazide. Spectral and elemental analysis confirmed the structure of the prepared derivatives 9-16. Also, as anticancer agents, the latter derivatives were screened against three human cancerous cell lines: human lung fibroblast (WI38), colorectal carcinoma colon cancer (HCT-116), and mammary gland breast cancer (MCF-7). Doxorubicin, a standard control, was used to compare viable cell percentages and IC50 values. In general, derivatives 12 and 16 revealed a higher potency against the three human cancerous cell lines. Finally, the molecular descriptors of compounds 12 and 16 were correlated with their observed cytotoxicity. result: In general, derivatives 12 and 16 revealed a higher potency against the three human cancerous cell lines.

Unveiling the anticancer potential: Exploring 4-fluoro benzoic acid and piperazine through spectroscopic, X-ray diffraction, DFT and molecular docking analysis

The crystalline substance formed from piperazine and 4-fluorobenzoic acid (PZ-PFBA) was successfully synthesized. This synthesis involved the transfer of protons between the selected acid and base, resulting in the formation of distinct crystalline salt. The SCXRD analysis conforms the salt crystallized in a monoclinic crystal system with a P 21/c space group and lattice parameters are a = 13.0688(14) Å, b = 8.2686(8) Å, and c = 8.2552(9) Å. Hirshfeld surface analysis, a technique for quantifying molecular interactions, was employed to investigate the prepared crystalline salt. Additionally, the salt was subjected to further examination using FT-IR, 1H NMR, 13C NMR, and SCXRD studies. The crystalline salt has major and established biological actions that inhibit the human lung cancer cell line A549. In vitro, and Insilico anticancer tests show that PZ-PFBA has better efficacy against the human cervical cancer cell line (HeLa) and in bioinformatics analysis. PZ-PFBA demonstrated more efficacy in reducing pathogenic strains compared to its parent reactants.

Synthesis, crystal structures and antiproliferative activities of a new indole-containing dipyridylmethanone hydrazone Schiff base and its cadmium(II) complex.

In this study, we introduce a novel indole-containing pyridine-based Schiff base, (E)-2-({[bis(pyridin-2-yl)methylidene]hydrazin-1-ylidene}methyl)-1H-indole, C20H15N5 (2-DPHI), and its cadmium(II) complex poly[[2-({[bis(pyridin-2-yl)methylidene]hydrazin-1-ylidene}methyl)-1H-indole]di-μ-chlorido-cadmium(II)], [CdCl2(C20H15N5)]n (pCd2), as potential anticancer agents. The Schiff base was synthesized by reacting dipyridylmethanone hydrazone with indole-2-formaldehyde, while the cadmium complex was prepared by combining CdCl2 and 2-DPHI in methanol at room temperature. Both compounds were evaluated for their cytotoxicity against three human cancer cell lines (A375, A549 and HeLa) and a normal cell line (HFF-1). The ligand 2-DPHI exhibited notable antitumour activity, with an IC50 value of 12.22 µM against A375 and 15.17 µM against A549 after 48 h, while the pCd2 complex showed an even stronger inhibition of A375 cells, with an IC50 value of 4.88 µM, outperforming both 2-DPHI and CdCl2. Both compounds demonstrated lower toxicity towards normal cells compared to cancer cells. The structures of 2-DPHI and pCd2 were fully characterized using single-crystal X-ray diffraction, elemental analysis, high-resolution mass spectrometry and FT-IR, 1H NMR, 13C NMR and UV-Vis spectroscopy.

Discovery of novel quinazoline derivatives as tubulin polymerization inhibitors targeting the colchicine binding site with potential anti-colon cancer effects

Tubulin is a critical target for cancer therapy, with colchicine binding site inhibitors (CBSIs) being the most extensively researched. A series of quinazoline derivatives designed to target the colchicine binding site of tubulin were synthesized and evaluated for their biological activities. The antiproliferative effects of these compounds were tested against six human cancer cell lines, and compound Q19 demonstrated potent antiproliferative activity against the HT-29 cell line, with an IC50 value of 51 nM. Additionally, further investigation revealed that Q19 effectively inhibited microtubule polymerization by binding to the colchicine binding site on tubulin. Furthermore, compound Q19 arrested the HT-29 cell cycle at the G2/M phase, induced apoptosis in these cells, and disrupted angiogenesis. Finally, compound Q19 exhibited potent inhibitory effects on tumor growth in HT-29 xenografted mice while demonstrating minimal toxic side effects and acceptable pharmacokinetic properties. These findings suggested that Q19 hold promise as a potential candidate for colon cancer therapy targeting tubulin.