Promising Cytotoxicity Research Articles

A Study of the Bioactive Compounds, Antioxidant Capabilities, Antibacterial Effectiveness, and Cytotoxic Effects on Breast Cancer Cell Lines Using an Ethanolic Extract from the Aerial Parts of the Indigenous Plant Anabasis aretioïdes Coss. & Moq.

Anabasis aretioïdes contain numerous bioactive compounds that provide several advantages, including antioxidant, antibacterial, anticancer, neuroprotective, anti-inflammatory, and antidiabetic characteristics. This study aimed to make a hydroethanolic extract from the aerial part of the plant, analyze its biochemical compounds, and test its biological activities. From HPLC-DAD analysis, cinnamic acid, sinapic acid, and vanillin bioactives were found to be the main compounds in the extract. The spectrometric tests revealed that the extract was rich in flavonoids (8.52 ± 0.32 mg RE/100 g DW), polyphenols (159.32 ± 0.63 mg GAE/100 g DW), and condensed tannins (8.73 ± 0.23 mg CE/100 g DW). The extract showed significant antioxidant activity. There were strong correlations between the amount of flavonoid or polyphenol and the antioxidant assays, including ABTS, DPPH, β-carotene, and TAC. The extract also showed highly effective results against Gram-positive bacteria Staphylococcus aureus and Enterococcus faecalis as well as against Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, and showed promising cytotoxicity against breast cancer cell lines MCF-7 and MDA-MB-231. The in silico modeling of the bioactive compounds contained in the extract illustrated their interaction mode with the active sites of particular target proteins, and it showed that rutin had the strongest effect on stopping NADPH oxidase enzyme, with a glide score of −6.889 Kcal/mol. Sinapic acid inhibited E. coli beta-ketoacyl-[acyl carrier protein] synthase (−7.517 kcal/mol), and apigenin showed high binding affinity to S. aureus nucleoside di-phosphate kinase, with −8.656 kcal/mol. Succinic acid has the strongest anticancer effect for caspase-3, with a glide score of −8.102 kcal/mol. These bioactive components may be beneficial as antioxidant and antibacterial applications in medicine, foods, natural cosmetics, and breast cancer prevention in the future. As a result, the use of this indigenous plant must be considered to maximize its value and preservation.

Discovery of New Thiourea Derivatives as Potential SIRT Inhibitors

Objective: This study aimed to design and synthesize novel thiourea-based compounds targeting Sirtuins (SIRTs), a class of histone deacetylase enzymes implicated in various cellular processes, including cancer, and to evaluate their cytotoxic potential against colon cancer cells. Methods: Virtual modeling and molecular docking studies were conducted to design the compounds and assess their interaction with SIRT enzymes. Compounds showing acceptable docking scores were selected for organic synthesis. The final compounds (MA-1 to MA-6) were synthesized and characterized using FTIR, ¹H-NMR, and ¹³C-NMR spectroscopy. Cytotoxicity studies were performed on SW480 colon cancer cells to evaluate the biological activity of the synthesized compounds. Results: All synthesized compounds exhibited promising cytotoxicity against SW480 colon cancer cells, with MA-2 demonstrating a particularly strong effect. The half-maximal inhibition concentration (IC50) of the compounds was in the single-digit micromolar range, comparable to established SIRT inhibitors Selisistat and AGK2. Conclusion: The thiourea-based compounds synthesized in this study, especially MA-2, showed significant potential as SIRT inhibitors with cytotoxic activity against colon cancer cells. These results warrant further investigation into their therapeutic potential.

Organotin(IV) complexes of tridentate (ONO) hydrazone ligands: synthesis, spectral characterization, antituberculosis, antimicrobial, anti-inflammatory, molecular docking and cytotoxicity studies.

Infectious diseases have a significant impact in the historical trajectory of humanity, exerting profound influence on societies, driving advancements in medical science, and significantly impacting individuals on a worldwide scale. Consequently, this research endeavours to identify potent agents combatting tuberculosis, inflammation, and microbial deformities. The investigation focuses on hydrazones (1,2) endowed eight organotin(IV) complexes, where hydrazones were derived from 2-acetyl-1H-indene-1,3(2H)-dione and 2-phenoxypropanehydrazide/2-(2,4-dichlorophenoxy)propanehydrazide. All compounds underwent thorough characterization utilizing a variety of spectral and analytical techniques including, multinuclear NMR, FT-IR, HRMS, UV-Vis, SEM-EDAX, TGA, XRD, molar conductance measurements, establishing the pentacoordinated environment around tin(IV) ion with tridentate (ONO) mode of chelation of hydrazones. Powder XRD revealed the ligand's crystalline and complexes' semi-crystalline nature, while thermal analysis indicated two-step decomposition leaving tin oxide residue. In vitro evaluations utilize microplate alamar blue assay for assessing anti-tuberculosis activity, serial dilution technique for antimicrobial efficacy, and bovine serum albumin method for evaluating anti-inflammatory properties. The complexes exhibited higher biological activities than their respective ligands and the activity of the complexes follow the order: Ph2SnL1-2 > Bu2SnL1-2 > Et2SnL1-2 > Me2SnL1-2. Among them, phenyl complex (10) [Ph2SnL2] displays superior efficacy against TB dysfunction (MIC: 0.0180 ± 0.009μmol/mL) and also demonstrates exceptional potency in combating inflammation (IC50: 7.27 ± 0.04μM), and microbial (MIC: 0.0045μmol/mL) infections, comparable to standard drugs. Additionally, cytotoxicity testing against vero cell line revealed decreased toxicity at lower concentrations, and attenuated by chelation. Phenyl complex (10) [Ph2SnL2] shows promising cytotoxicity at 3.12µg/mL (19.29 ± 0.09%). Further, The diphenyltin(IV) complex (10), identified as the most effective against TB, shows stronger binding to key 3PTY protein residues (-42.2kJ/mol) compared to ligand (2) (-33.4kJ/mol), correlating with its superior anti-tuberculosis potency in biological assays. This comprehensive approach aims to actively contribute to ongoing initiatives addressing infectious diseases, thereby advancing global health and overall well-being.

Branched oncolytic peptides target HSPGs, inhibit metastasis, and trigger the release of molecular determinants of immunogenic cell death in pancreatic cancer.

Immunogenic cell death (ICD) can be exploited to treat non-immunoreactive tumors that do not respond to current standard and innovative therapies. Not all chemotherapeutics trigger ICD, among those that do exert this effect, there are anthracyclines, irinotecan, some platinum derivatives and oncolytic peptides. We studied two new branched oncolytic peptides, BOP7 and BOP9 that proved to elicit the release of damage-associated molecular patterns DAMPS, mediators of ICD, in pancreatic cancer cells. The two BOPs selectively bound and killed tumor cells, particularly PANC-1 and Mia PaCa-2, but not cells of non-tumor origin such as RAW 264.7, CHO-K1 and pgsA-745. The cancer selectivity of the two BOPs may be attributed to their repeated cationic sequences, which enable multivalent binding to heparan sulfate glycosaminoglycans (HSPGs), bearing multiple anionic sulfation patterns on cancer cells. This interaction of BOPs with HSPGs not only fosters an anti-metastatic effect in vitro, as demonstrated by reduced adhesion and migration of PANC-1 cancer cells, but also shows promising tumor-specific cytotoxicity and low hemolytic activity. Remarkably, the cytotoxicity induced by BOPs triggers the release of DAMPs, particularly HMGB1, IFN-β and ATP, by dying cells, persisting longer than the cytotoxicity of conventional chemotherapeutic agents such as irinotecan and daunorubicin. An in vivo assay in nude mice showed an encouraging 20% inhibition of tumor grafting and growth in a pancreatic cancer model by BOP9.

Biosynthesis of Atypical Angucyclines Unveils New Ring Rearrangement Reactions Catalyzed by Flavoprotein Monooxygenases.

Six new angucycline structures, including spirocyclione A (1), which contains an unusual oxaspiro[5.5]undecane architecture, and its ring-A-cleaved product spirocyclione B (2), were discovered by heterologous expression of a type II polyketide biosynthetic gene cluster captured from a marine actinomycete strain Streptomyces sp. HDN155000. Three flavoprotein monooxygenases are confirmed to be responsible for the oxidative carbon skeleton rearrangements in the biosynthesis of compounds 1 and 2. The obtained compounds showed promising cytotoxicity against different types of cancer cells.

Palladium(II)-Indenyl Complexes Bearing N-Heterocyclic Carbene (NHC) Ligands as Potent and Selective Metallodrugs toward High-Grade Serous Ovarian Cancer Models.

In this study, we synthesized novel Pd(II)-indenyl complexes using various N-heterocyclic carbene (NHC) ligands, including chelating NHC-picolyl, NHC-thioether, and diNHC ligands, and two monodentate NHCs. Transmetalation reactions between a Pd(II)-indenyl precursor and silver-NHC complexes were generally employed, except for chelating diNHC derivatives, which required direct reaction with bisimidazolium salts and potassium carbonate. Characterization included NMR, HRMS analysis, and single-crystal X-ray diffraction. In vitro on five ovarian cancer cell lines showed notable cytotoxicity, with IC50 values in the micro- and submicromolar range. Some compounds exhibited intriguing selectivity for cancer cells due to higher tumor cell uptake. Mechanistic studies revealed that monodentate NHCs induced mitochondrial damage while chelating ligands caused DNA damage. One chelating NHC-picolyl ligand showed promising cytotoxicity and selectivity in high-grade serous ovarian cancer models, supporting its consideration for preclinical study.

Antitumor Activity of New Pd(II) Complexes with Ligands Derived from O‐Vanillin Acting as Topoisomerase I and II Inhibitors

AbstractThis study investigates topoisomerase I and II enzyme inhibition by novel Pd(II) complexes. TSC represents the chelating ligand thiosemicarbazone, which is modified at its 4(N)‐nitrogen terminal position with substituents such as C2H5, CH3, and H. PR3 represents the triphenylphosphine ligand, with positional variations including para substituents H, F, OCH3, and CH3. The aim is to establish a correlation between these molecular variations and cytotoxicity. In particular, the compounds show promising cytotoxicity against MDA‐MB‐231 and A549 tumor cell lines, especially those with H substitution at the terminal position 4(N) of TSC and H and F in the triphenylphosphine. The results suggest that a smaller molecular volume of ligand substituents may enhance the cytotoxic effects. The inhibitory potential of the complexes against DNA topoisomerase enzymes was investigated. The IC₅₀ values of the most promising complexes strongly inhibit TOPOIIα and TOPOIβ, suggesting these enzymes as primary targets. These complexes exhibited significantly lower IC₅₀ values (4.32–4.88 μM) compared to cisplatin (10.2 μM) against MDA‐MB‐231 cells, indicating a distinct mode of action. However, it is noteworthy that the complexes did not inhibit the action of DNA topoisomerase IIβ, suggesting selectivity against specific isoforms of DNA topoisomerase II that act as catalytic inhibitors.

Brønsted Acid Catalyzed Asymmetric Synthesis of Cyclopentenones with C4-Quaternary Centers Starting from Vinyl Sulfoxides and Allenyl Ketones or Allenoates.

Starting with chiral vinyl sulfoxides and allenyl ketones or allenoates, a triflic acid-catalyzed asymmetric [3,3]-sigmatropic rearrangement of sulfoniums is reported to have a direct access to highly functionalized C4-chiral cyclopentenones (19 examples, up to 85% yield and >95% enantiomeric excesses). In addition to the use of these chiral compounds as key building blocks in organic synthesis, the antiproliferative activities of sulfoxide substrates and the corresponding cyclopentenones were evaluated, and promising cytotoxicity against the HL-60 human tumor cell line was found.

Synthesis of novel piperazine-based bis(thiazole)(1,3,4-thiadiazole) hybrids as anti-cancer agents through caspase-dependent apoptosis.

A series of novel piperazine-based bis(thiazoles) 13a-d were synthesized in moderate to good yields via reaction of the bis(thiosemicarbazones) 7a, b with an assortment of C-acetyl-N-aryl-hydrazonoyl chlorides 8a-f. Similar treatment of the bis(thiosemicarbazone) 7a, b with C-aryl-N-phenylhydrazonoyl chlorides 10a, b afforded the expected bis(thiadiazole) based piperazine products 13b-d in reasonable yields. Cyclization of 7a, b with two equivalents of α-haloketones 14a-d led to the production of the corresponding bis(4-arylthiazol)piperazine derivatives 15a-h in good yields. The structures of the synthesized compounds were confirmed from elemental and spectral data (FTIR, MALDI-TOF, 1H, and 13C NMR). The cytotoxicity of the new compounds was screened against hepatoblastoma (HepG2), human colorectal carcinoma (HCT 116), breast cancer (MCF-7), and Human Dermal Fibroblasts (HDF). Interestingly, all compounds showed promising cytotoxicity against most of the cell lines. Interestingly, compounds 7b, 9a, and 9i exhibited IC50 values of 3.5, 12.1, and 1.2 nM, respectively, causing inhibition of 89.7%, 83.7%, and 97.5%, compared to Erlotinib (IC50 = 1.3 nM, 97.8% inhibition). Compound 9i dramatically induced apoptotic cell death by 4.16-fold and necrosis cell death by 4.79-fold. Compound 9i upregulated the apoptosis-related genes and downregulated the Bcl-2 as an anti-apoptotic gene. Accordingly, the most promising EGFR-targeted chemotherapeutic agent to treat colon cancer was found to be compound 9i.

Investigation on the Anticancer Activity of [6]-Gingerol of Zingiber officinale and its Structural Analogs against Skin Cancer.

Skin cancer is the most common type of cancer caused by the uncontrolled growth of abnormal cells in the epidermis and the outermost skin layer. This study aimed to study the anti-skin cancer potential of [6]-Gingerol and 21 related structural analogs using in vitro</i> and in silico</i> studies. The ethanolic crude extract of the selected plant was subjected to phytochemical and GC-MS analysis to confirm the presence of the [6]-gingerol. The anticancer activity of the extract was evaluated by MTT (3-[4, 5-dimethylthiazol-2-y]-2, 5-diphenyl tetrazolium bromide) assay using the A431 human skin adenocarcinoma cell line. The GC-MS analysis confirmed the presence of [6]-Gingerol compound, and its promising cytotoxicity IC50 was found at 81.46 ug/ml in the MTT assay. Furthermore, the in silico studies used [6]-Gingerol and 21 structural analogs collected from the PubChem database to investigate the anticancer potential and drug-likeliness properties. Skin cancer protein, DDX3X, was selected as a target that regulates all stages of RNA metabolism. It was docked with 22 compounds, including [6]-Gingerol and 21 structural analogs. The potent lead molecule was selected based on the lowest binding energy value. Thus, the [6]-Gingerol and its structure analogs could be used as lead molecules against skin cancer and future drug development process.

Evaluation of Spirooxindole-3,3'-pyrrolines-incorporating Isoquinoline Motif as Antitumor, Anti-Inflammatory, Antibacterial, Antifungal, and Antioxidant Agents.

A series of novel 2-(isoquinolin-1-yl)-spiro[oxindole-3,3'-pyrrolines] were synthesized by a one-pot three-component reaction involving dimethyl acetylenedicarboxylate, 3- phenylimidazo[5,1-a]isoquinoline and N-alkylisatins in chloroform at ∼60 °C for 24 h. This study aimed at the synthesis of novel spirooxindole-3,3'-pyrrolines derivatives and in vitro evaluation of cytotoxicity affinities in cross-correlations with their antiinflammation and radical scavenging capacities. The objective of this study was to use a one-pot, three-component reaction to synthesize a novel set of spirooxindole-3,3'-pyrrolines derivatives. A novel set of spirooxindole-3,3'-pyrrolines (8a-i) was synthesized by a one-pot threecomponent reaction involving dimethyl acetylenedicarboxylate, 3-phenylimidazo[5,1-a]isoquinoline and N-alkylisatins in chloroform at ∼60 °C for 24 h. These new compounds were characterized by 1HNMR, 13C-NMR, and HRMS spectral data and screened for their antitumor, anti-inflammatory, antibacterial, antifungal, and antioxidant activities. The new synthetic spirooxindole-3,3'-pyrrolines (8a-i)-tested compounds displayed significant anti-inflammatory properties and were noncytotoxic on PDL fibroblasts. However, they lacked antioxidative-DPPH radical scavenging capabilities. Notably, Doxorubicin and cisplatin demonstrated antiproliferative effects on various cancer monolayers. Moreover, compounds 8b, 8d, 8f, 8h, and 8i exhibited pronounced viability reduction properties in colorectal and pancreatic cancer monolayers, as well as across skin, lung, prostate, and cervical adenocarcinomas, with higher cytotoxicity in mammary cancer cells MCF7 and T47D. None of the tested compounds had significant antibacterial activity against S. aureus or E. coli. However, compounds 8c, 8d, and 8f exhibited notable antifungal properties, indicating potential for further investigation. Eight new synthetic spiro[indoline-3,3-pyrroles] were prepared, characterized, and evaluated for their anti-inflammatory and cytotoxic properties. The compounds showed significant anti-inflammatory effects and promising cytotoxicity against various cancer monolayers, especially in colorectal and pancreatic cancers. Some compounds also exhibited antifungal properties. However, they did not exhibit significant antibacterial activity.

Biological Applications, In Vitro Cytotoxicity, Cellular Uptake, and Apoptotic Pathway Studies Induced by Ternary Cu (II) Complexes Involving Triflupromazine with Biorelevant Ligands.

The novel mixed-ligand complexes derived from the parent antidepressant phenothiazine drug triflupromazine (TFP) were synthesized along with the secondary ligands glycine and histidine. [Cu(TFP)(Gly)Cl]·2H2O (1) and [Cu(TFP)(His)Cl]·2H2O (2) were examined for their in vitro biological properties. Cyclic voltammetry was used to study the binding of both complexes to CT-DNA. The two complexes were examined for antiviral, antiparasite, and anti-inflammatory applications. An in vitro cytotoxicity study on two different cancer cell lines, MCF-7, HepG2, and a normal cell line, HSF, shows promising selective cytotoxicity for cancer cells. An investigation of the cell cycle and apoptosis rates was evaluated by flow cytometry with Annexin V-FITC/Propidium Iodide (PI) staining of the treated cells. Gene expression and western blotting were carried out to determine the expression levels of the pro-apoptotic markers and the anti-apoptotic marker Bcl2. The tested complexes decreased cell viability and triggered apoptosis in human tumor cell lines. Molecular docking was also used to simulate Bcl2 inhibition. Finally, complex (2) has potent antitumor effects on human tumor cells, especially against HepG2 cells, as seen in the cellular drug uptake assay. Consequently, complex (2) may prove useful against cancer, especially liver cancer. For further understanding, it needs to be explored in vivo.

Understanding adsorption ability of CNT (6, 6-6) and BNNT (6, 6-7) nanotubes for a novel hybrid pyrazole-indole drug, InPy-7a

The quest for enhanced drug delivery efficacy across diverse physiological conditions has spurred the exploration of various nanomaterials, including carbon-based materials like carbon nanotubes (CNTs) and boron nitride nanotubes (BNNTs). These materials offer high surface areas conducive to increased drug loading, with considerations such as surface charge, size, shape, and biocompatibility being paramount. The hybrid drug, synthesized by combining indole derivatives with a pyrazole moiety, has shown promising cytotoxicity against various cancer cell lines. In this context, we have explored the adsorption ability of CNT (6, 6-6) and BNNT (6, 6-7) nanotubes for a novel hybrid drug, InPy-7a, using density functional theory (DFT) calculations. Our study has aimed to elucidate the adsorption mechanisms and electronic properties of InPy-7a on the surfaces of CNT (6, 6-6) and BNNT (6, 6-7). Through computational tools, we have analyzed the geometry optimization of InPy-7a onto the nanotube surfaces, evaluating molecular interactions, quantum descriptors, frontier molecular orbitals (FMO), natural bond orbitals (NBO), nuclear magnetic resonance (NMR), and molecular electrostatic potential (MEP). Our results have illuminated the underlying mechanisms by revealing unique interactions and electronic changes during complexation. Based on predicted electronic aspects and molecular interactions, the CNT@InPy-7a-S5 complex system showed greater chemical reactivity, adsorption, and stability than BNNT@InPy-7a-S6. These findings open up opportunities for additional experimental validations and offer insightful information about the possible uses of drug delivery systems based on nanotubes.

Pharmacological Properties of White Mulberry (Morus alba L.) Leaves: Suppressing Migratory and Invasive Activities Against A549 Lung Cancer Cells.

Morus alba known as a white mulberry is a medicinal plant that has been used in food ingredients and traditional medicine. M. alba leaves contain various bioactive phenolic compounds, in particular chlorogenic acid (CGA), which is a major bioactive ingredient. Their anticancer potency of M. alba leaf extracts derived from Soxhlet extraction was evaluated based on cytotoxicity and antimigratory and antiinvasive properties. The dichloromethane extract exhibited the highest nitric oxide radical scavenging activity with a half-maximal inhibitory concentration (IC50) value of 780μg/mL, promising cytotoxicity against HuCCA-1, MCF-7, and A-549 cells with IC50 values of 59.18, 62.20, and 103.25μg/mL, respectively. CGA selectively inhibited the growth of MCF-7 cells with an IC50 value of 26.75μg/mL and showed potent radical scavenging activity against DPPH radicals (IC50 = 18.85μg/mL). An ethanolic extract derived from the gradient Soxhlet extraction suppressed A549 lung cancer cell migration and invasion more effectively than CGA with no migratory inhibition effect on noncancerous HaCaT cells. Furthermore, the ethanolic extract and CGA accelerated HaCaT wound closure at 20µg/mL, which was the same as allantoin. Bioactive ingredients including triterpenes, steroids, phenolics, and flavonoids were mainly detected in all extracts. The highest content of CGA (52.23g/100g dry weight) was found in the ethanolic extract derived from the gradient Soxhlet extraction. These findings show the potency of the dichloromethane extract as a cytotoxic agent against various cancer types and the ethanolic extract as an antimetastatic agent by their antimigratory and antiinvasive activities.

Green Synthesis and Characterization of Ginger-Derived Silver Nanoparticles and Evaluation of Their Antioxidant, Antibacterial, and Anticancer Activities.

The efficacy, targeting ability, and biocompatibility of plant-based nanoparticles can be exploited in fields such as agriculture and medicine. This study highlights the use of plant-based ginger nanoparticles as an effective and promising strategy against cancer and for the treatment and prevention of bacterial infections and related disorders. Ginger is a well-known spice with significant medicinal value due to its phytochemical constituents including gingerols, shogaols, zingerones, and paradols. The silver nanoparticles (AgNPs) derived from ginger extracts could be an important non-toxic and eco-friendly nanomaterial for widespread use in medicine. In this study, AgNPs were biosynthesized using an ethanolic extract of ginger rhizome and their phytochemical, antioxidant, antibacterial, and cytotoxic properties were evaluated. UV-visible spectral analysis confirmed the formation of spherical AgNPs. FTIR analysis revealed that the NPs were associated with various functional biomolecules that were associated with the NPs during stabilization. The particle size and SEM analyses revealed that the AgNPs were in the size range of 80-100 nm, with a polydispersity index (PDI) of 0.510, and a zeta potential of -17.1 mV. The purity and crystalline nature of the AgNPs were confirmed by X-ray diffraction analysis. The simple and repeatable phyto-fabrication method reported here may be used for scaling up for large-scale production of ginger-derived NPs. A phytochemical analysis of the ginger extract revealed the presence of alkaloids, glycosides, flavonoids, phenolics, tannins, saponins, and terpenoids, which can serve as active biocatalysts and natural stabilizers of metallic NPs. The ginger extracts at low concentrations demonstrated promising cytotoxicity against Vero cell lines with a 50% reduction in cell viability at 0.6-6 μg/mL. When evaluated for biological activity, the AgNPs exhibited significant antioxidant and antibacterial activity on several Gram-positive and Gram-negative bacterial species, including Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, and Staphylococcus aureus. This suggests that the AgNPs may be used against multi-drug-resistant bacteria. Ginger-derived AgNPs have a considerable potential for use in the development of broad-spectrum antimicrobial and anticancer medications, and an optimistic perspective for their use in medicine and pharmaceutical industry.

Synthesis, molecular docking studies and biological evaluation of N-(4-oxo-2-(trifluoromethyl)-4H-chromen-7-yl) benzamides as potential antioxidant, and anticancer agents

A series of novel chromone derivatives of (N-(4-oxo-2-(trifluoromethyl)-4H-chromen-6-yl) benzamides) were synthesized by treating 7-amino-2-(trifluoromethyl)-4H-chromen-4-one with K2CO3 and/or NaH, suitable alkyl halides and acetonitrile and/or 1,4-dioxane. The obtained products are in high yields (87 to 96%) with various substituents in short reaction times with no more by-products and confirmed by FT-IR, 1H, and 13C-NMR Spectral data. The in vitro cytotoxic activity was examined against two human cancer cell lines, namely the human lung adenocarcinoma (A-549) and the human breast (MCF-7) cancer cell line. Compound 4h showed promising cytotoxicity against both cell lines with IC50 values of 22.09 and 6.40 ± 0.26 µg/mL respectively, compared to that of the standard drug. We also performed the in vitro antioxidant activity by DPPH radical, hydrogen peroxide, NO scavenging, and total antioxidant capacity (TAC) assay methods, and they showed significant activities. The possible binding interactions of all the synthesized chromone derivatives are also investigated against selective pharmacological targets of human beings, such as HERA protein for cytotoxic activity and Peroxiredoxins (3MNG) for antioxidant activity which showed closer binding free energies than the standard drugs and evidencing the above two types of activities.

Oxindoline Containing Thiazolidine‐4‐one Tethered Triazoles Act as Antimitotic Agents by Targeting Microtubule Dynamics

AbstractOxindoline containing thiazolidine‐4‐ones linked triazole hybrids (24 a–l) series were synthesized by multistep synthesis and tested for their cytotoxic activity against four human cancer cell lines. Significantly higher susceptibility was observed in liver (HepG2) cancer cells. Among them conjugates 24 c and 24 e exhibited promising cytotoxicity with IC50 values of 1.64 μM, and 2.07 μM respectively when compared to the standard 5‐fluorouracil (IC50=20.8 μM) against the HepG2 cell line. Later on, these compounds changed the morphology of HepG2 cells and significantly inhibited colony formation in HepG2 in a dose‐dependent manner. The scratch assay divulged that these compounds decreased wound size and inhibited cell migration. Interestingly, they induced the cell cycle arrest at the S phase. Moreover, the DCFDA assay indicated ROS production proportionate to compound dose and AO/Eb staining revealed increased apoptotic cell count with higher doses. The tubulin polymerization assay reveals that they inhibited the microtubules and acted as antimitotic agents. In‐silico results of these conjugates also support their tubulin inhibitory properties. Interestingly, these compounds have adequate ADME‐toxicity parameters. Based on free energy calculation results, it was observed that these inhibitors influence the conformational flexibility of the target tubulin protein.

A green chemistry approach for preparation of metronidazole-zinc (ІІ) complexes: In vitro characterization, antimicrobial activity and promising cytotoxicity

Antibiotic-metal complexes attract the attention of pharmaceutical scientists who endeavor to increase the activity of antibiotics currently in use as those looking for new compounds possessing modified pharmacological and toxicological properties. This research proposed enhanced antimicrobial and cytotoxic activities of metronidazole and reduced irritancy of zinc chloride through complexation. The chemically green preparation of metronidazole: zinc (ІІ) complexes with different ratios: (A; 2:1), (B; 1:1) and (C; 1:2), revealed the formation of three complexes. The differences between their structures, physical and chemical properties were evaluated using morphological characteristics, DSC, XRD, FTIR, Mass spectrometry, and UV–Vis spectroscopy. The antimicrobial activities of the complexes were increased when compared to the parent drug where complex-C manifested the highest antibacterial activity (MIC = 0.625 mM and 10 mM for the bacterial strains and C. albicans, respectively). The antitumor efficacy of the complexes was studied against HepG2 and MCF-7 human cancer cell lines. Complex-A showed the highest cytotoxicity against HepG2 cells (IC50 = 17.2 μM), while, complex-C displayed the most cytotoxic activity against MCF-7 cells (IC50 = 29.0 μM). The in vivo skin irritancy study of the complexes on rats and their histological examination were assessed and showed no erythema and/or edema. Our results suggest the promising antimicrobial and antitumor activity of the prepared metronidazole-zinc complexes.

Platinum(0)-η2-1,2-(E)ditosylethene Complexes Bearing Phosphine, Isocyanide and N-Heterocyclic Carbene Ligands: Synthesis and Cytotoxicity towards Ovarian and Breast Cancer Cells.

A wide range of platinum(0)-η2-(E)-1,2-ditosylethene complexes bearing isocyanide, phosphine and N-heterocyclic carbene ancillary ligands have been prepared with high yields and selectivity. All the novel products underwent thorough characterization using spectroscopic techniques, including NMR and FT-IR analyses. Additionally, for some compounds, the solid-state structures were elucidated through X-ray diffractometry. The synthesized complexes were successively evaluated for their potential as anticancer agents against two ovarian cancer cell lines (A2780 and A2780cis) and one breast cancer cell line (MDA-MB-231). The majority of the compounds displayed promising cytotoxicity within the micromolar range against A2780 and MDA-MB-231 cells, with IC50 values comparable to or even surpassing those of cisplatin. However, only a subset of compounds was cytotoxic against cisplatin-resistant cancer cells (A2780cis). Furthermore, the assessment of antiproliferative activity on MRC-5 normal cells revealed certain compounds to exhibit in vitro selectivity. Notably, complexes 3d, 6a and 6b showed low cytotoxicity towards normal cells (IC50 > 100 µM) while concurrently displaying potent cytotoxicity against cancer cells.

Exploring pyrrolidinyl-spirooxindole natural products as promising platforms for the synthesis of novel spirooxindoles as EGFR/CDK2 inhibitors for halting breast cancer cells.

Cancer represents a global challenge, and the pursuit of developing new cancer treatments that are potent, safe, less prone to drug resistance, and associated with fewer side effects poses a significant challenge in cancer research and drug discovery. Drawing inspiration from pyrrolidinyl-spirooxindole natural products, a novel series of spirooxindoles has been synthesized through a one-pot three-component reaction, involving a [3 + 2] cycloaddition reaction. The cytotoxicity against breast cancer cells (MCF-7 and MDA-MB-231) and safety profile against WISH cells of the newly developed library were assessed using the MTT assay. Compounds 5l and 5o exhibited notable cytotoxicity against MCF-7 cells (IC50 = 3.4 and 4.12μM, respectively) and MDA-MB-231 cells (IC50 = 8.45 and 4.32μM, respectively) compared to Erlotinib. Conversely, compounds 5a-f displayed promising cytotoxicity against MCF-7 cells with IC50 values range (IC50 = 5.87-18.5μM) with selective activity against MDA-MB-231 cancer cells. Compound 5g demonstrated the highest cytotoxicity (IC50 = 2.8μM) among the tested compounds. Additionally, compounds 5g, 5l, and 5n were found to be safe (non-cytotoxic) against WISH cells with higher IC50 values ranging from 39.33 to 47.2μM. Compounds 5g, 5l, and 5n underwent testing for their inhibitory effects against EGFR and CDK-2. Remarkably, they demonstrated potent EGFR inhibition, with IC50 values of 0.026, 0.067, and 0.04μM and inhibition percentages of 92.6%, 89.8%, and 91.2%, respectively, when compared to Erlotinib (IC50 = 0.03 μM, 95.4%). Furthermore, these compounds exhibited potent CDK-2 inhibition, with IC50 values of 0.301, 0.345, and 0.557μM and inhibition percentages of 91.9%, 89.4%, and 88.7%, respectively, in contrast to Roscovitine (IC50 = 0.556 μM, 92.1%). RT-PCR analysis was performed on both untreated and 5g-treated MCF-7 cells to confirm apoptotic cell death. Treatment with 5g increased the gene expression of pro-apoptotic genes P53, Bax, caspases 3, 8, and 9 with notable fold changes while decreasing the expression of the anti-apoptotic gene Bcl-2. Molecular docking and dynamic simulations (100 ns simulation using AMBER22) were conducted to investigate the binding mode of the most potent candidates, namely, 5g, 5l, and 5n, within the active sites of EGFR and CDK-2.