Potent Cytotoxic Activity Research Articles

Evaluation of the antitrypanosomal activity, cytotoxicity and phytochemistry of red Brazilian propolis.

Recently, the growth in the consumption of functional foods with potential nutritional and health benefits revealed rapid progress in phytochemical analysis to assure quality and profile the chemical composition. Bee propolis, a gummy exudate produced in beehives after harvesting from different plant species and showed to contain bioactive secondary metabolites with biological importance. The main goal of the current study is to profile the chemical composition of red propolis samples from the Brazilian stingless bee Tetragonula biroi for the first time using HPLC-UV-ELSD and NMR analysis for assignment of the abundant metabolites' classes as well as extraction and isolation of the major compounds. Column chromatography and size exclusion chromatography were applied for the purification of the major compounds in red Brazilian propolis. Further, testing the antitrypanosomal and cytotoxic activities against Trypanosoma brucei and human leukemia cell lines (U937) was performed. A total of 29 secondary metabolites were identified as two anthocyanins, 6 flavonoids, 8 isoflavonoids, 10 phenolics, two phenolic acids, and one triterpenoid. Two phenolic compounds were purified and identified using 1D and 2D NMR analysis along with MS analysis as liquiritigenin and calycosin. Red Brazilian propolis FB-3 fraction showed the highest inhibitory activity against T. brucei at 1.6 μg/ml, compared to 12.4 μg/ml of the crude extract. The isolated compounds showed moderate activity with an MIC of 8.5 μg/ml for liquiritigenin and 8.7 μg/ml for calycosin. Moreover, FB-3 fraction and calycosin were showed the potent cytotoxic effect with IC50 = 45.1 and 35.8μg/ml, respectively compared to IC50 = 29.5 μg/ml of the standard diminazen. Hence, red Brazilian propolis is rich source of polyphenols with myriad biological importance. Propolis fractions and purified compounds showed moderate antiprotozoal activity and potent cytotoxic activity against human leukemia cell lines.

Synthesis of epoxyazadiradione-thiazole hybrid derivatives and evaluation of their cytotoxic activities

In an attempt to develop natural product-based anticancer agents, a series of novel epoxyazadiradione-thiazole hybrids (6a-j) were synthesised and evaluated for their anticancer activity. All the synthesised derivatives were assessed for in vitro cytotoxic activity against a panel of human cancer and normal cell lines and the results showed that most of the compounds exhibited significant cytotoxic activity against cancer cells and as well some of the compounds showed less cytotoxicity against normal cells. In particular, compound 4 showed potent cytotoxic activity against tongue cancer cell lines. In consideration of the potent activity, the compound 4 was further assessed for cell cycle analysis and the results showed that the compound arrests the cell cycle progression at the G0/G1 phase in the tongue cancer cell lines. Consequently, the annexin V/PI staining assay demonstrated that compound 4 induced early apoptosis against tongue cancer. Taken together, the results inferred that the epoxyazadiradione is promising anticancer candidate for developing novel anticancer drugs against tongue cancer.

Bioactive secondary metabolites from fungal endophytes, Penicillium oxalicum and Phoma herbarum, associated with Morus nigra and Ficus sycomorus: an in silico study.

Two pure fungal strains were isolated and identified from Ficus sycomorus and Morus nigra, namely, Penicillium oxalicum (OR673586) and Phoma herbarum (OR673589), respectively. The extract and fractions of secondary metabolites of each fungus were evaluated for antioxidant, anti-inflammatory, antimicrobial, antibiofilm, antidiabetic, and cytotoxic activities. The chloroform fraction of P. oxalicum showed potent cytotoxic activity (IC50 = 7.695 μg mL-1) against Hep-G2 cell line, alongside moderate antioxidant and anti-inflammatory activities. On the other hand, the P. herbarum chloroform fraction showed potent antioxidant (DPPH IC50 = 5.649 μg mL-1) and antidiabetic activities (IC50 = 14.91 μg mL-1) against inhibition of α-glucosidase, in addition to moderate cytotoxicity, anti-inflammatory, and antimicrobial activities. Guided cytotoxic fractionation leads to identifying bioactive compounds using hyphenated techniques. LC-MS identified fourteen compounds for P. herbarum and thirteen compounds for P. oxalicum. Three known compounds, mevalolactone (1), glycerol monolinoleate (3), and ergosterol (7) in addition to one new compound, barcelonyl acetate (2), were isolated from P. herbarum. On the other hand, four known compounds, 4-hydroxyphenyl acetic acid (4), secalonic acid D (5), altersolanol A (6), and ergosterol (7), were isolated from P. oxalicum. Altersolanol A (6) and secalonic acid D (7) exhibited outstanding cytotoxic activity against Hep-G2 and Caco-2 cell lines, with IC50 values ranging from 0.00038 to 0.208 μM. In silico study findings showed altersolanol A (6), 4-hydroxyphenyl acetic acid (4), glycerol monolinoleate (3), and barcelonyl acetate (2) displayed significant potential but may benefit from further optimization as lead for developing potent c-Jun N-terminal kinase 2 (JNK2, PDB: 3NPC) inhibitors, potentially leading to novel therapeutic strategies targeting cancer therapy.

Structurally diverse bufadienolides from the skins of Bufo bufo gargarizans and their cytotoxicity

Natural products, with their extensive chemical diversity, distinctive biological activities, and vast reservoirs, provide a robust foundation for advancing cancer therapeutics. A comprehensive phytochemical investigation of the skins from Bufo bufo gargarizans afforded two new bufadienolide derivatives identified as bufalactamides A and B (1–2), along with six known compounds: argentinogenin (3), desacetylcinobufagin (4), desacetylcinobufaginol (5), cinobufaginol (6), bufalin (7) and gamabufalin (8). The structural elucidation of these compounds was meticulously carried out by analyses of spectroscopic data (1D and 2D NMR, HR-ESIMS), and comparison with the literature data. Plausible biosynthetic pathways for the new compounds were also discussed. Moreover, the cytotoxicity of the compounds was investigated using various cancer cell lines, including lung cancer (A549), colon cancer (HCT-116), liver cancer (SK-Hep-1), and ovarian cancer (SKOV3). Our research findings indicated that compounds 3, and 6–8 exhibit potent cytotoxic activity (IC50 < 2.5 µM). In contrast, compounds 4 and 5 display moderate cytotoxic activity (IC50 < 50 µM) while compounds 1 and 2 show no cytotoxic activity (IC50 > 100 µM). From this data, we conducted a comprehensive analysis of the structure-activity relationships among these compounds.

Carob Seeds as a Source of Bioactive Flavonoid Derivatives: Isolation, Network Pharmacology-guided Anti-cancer Activity, and HPLC Standardization.

Carob, Ceratonia siliqua L. (CS), is a legume well-known for its edible pod pulp. Its seeds are used almost exclusively as a source of the food additive E410. Although a variety of metabolites have been identified by HPLC and LC-MS analysis in CS, reports concerned with their isolation are scarce. In this study, two flavonoid derivatives were isolated from the methanolic extract of CS seeds, namely, quercetin-3-O-rhamnoside and 4'-p-hydroxybenzoylisorhamnetin-3,7-di-O-rhamnoside. Network pharmacology was unusually used as a guide for estimation of the biological potential of the isolated compounds. Finally, the methanolic extract of CS seeds and its ethyl acetate fraction were standardized for their 4'-p-hydroxybenzoylisorhamnetin-3,7-di-O-rhamnoside content by HPLC. The identified isolates displayed the ability to interfere with the activity of several target proteins associated with renal and colon cancers. Their cytotoxic effect on renal and colorectal cancer cell lines was investigated in comparison to Doxorubicin. The selectivity of the isolated compounds was evaluated on normal human fetal fibroblast cell lines. The isolated 4'-p-hydroxybenzoylisorhamnetin-3,7-di-O-rhamnoside showed very potent cytotoxic activity against the tested cell lines with the highest selectivity. CS seeds can be used as a source of bioactive flavonoid derivatives that can be incorporated in pharmaceutical industries.

Madecassic acid analogues with a five-membered A-ring and their cytotoxic activity

The structural modification of madecassic acid focused on the contraction of the six-membered A-ring to a five-membered ring, combined with the dehydration of 6-OH to form a new double bond and formation of the esterification or amidation at C-28. The synthesised structures were identified based on the analysis of their NMR and EIS-MS data. Eighteen new madecassic acid analogues were tested in vitro for their cytotoxicity against three cancer cell lines, including human mouth carcinoma (KB), human hepatocellular carcinoma (HepG2), and human lung carcinoma (A549) using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Among them, compounds 5 and 12 exhibited potent and selective cytotoxic activity in KB and HepG2 cell lines, with IC50 values ranging from 3.57 to 6.32 µM. The results also indicated that analogues with a 5-membered A-ring containing an α,β-unsaturated aldehyde esterified at C-23 showed a decrease in their cytotoxic activity compared to precursors in the tested cancer cells.

Cytotoxic Effects of Hibiscus surattensis L. Leaves Extracts on BSLT, MCF-7 and Hela Cells

Hibiscus surattensis L. leaves have been known as a folk medicine. Several previous reports have shown several potential therapeutic effects, including antidiabetic, antibacterial, anti-diarrheal, analgesic, hepatoprotective, and antioxidant, but no toxicity study is similar to the current one. Therefore, it is necessary to investigate the cytotoxic effect of these commonly consumed medicinal leaves. This study aimed to investigate the cytotoxicity of Hibiscus surattensis L. leaves extract (HSL). The cytotoxic effect was determined through brine shrimp lethality bioassay (BSLT) and in vitro Presto Blue assay of MCF-7 and Hela cell. HSL extract was obtained by maceration using 96% ethanol. The BSLT results showed that the HSL has LC50 value of 224.814 μg/mL. MTT assay results showed the IC50 value of the HSL extract on MCF-7 cells was 1419.83 μg/mL, and Hela cells were 2050.50 μg/mL. Based on the LC50 value that has been analyzed against HSL extract shows an LC50 value of less than 1000 μg/mL which can be concluded while having potential cytotoxic activity against experimental animal larvae of A. salina Leach. The results of the cytotoxic test with Presto Blue assay on two cancer cells used showed that the HSL extract was not toxic.

Design, in silico studies and biological evaluation of novel chalcones tethered triazolo[3,4-a]isoquinoline as EGFR inhibitors targeting resistance in non-small cell lung cancer

A novel series of six [1,2,4]triazolo[3,4-a]isoquinolin-3-yl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)prop-2-en-1-ones (3a–3f) was designed and synthesized. They were characterized based on spectral and elemental analyses. In silico studies were also committed to provide insights and a better understanding of their structural features. The six compounds were screened for their antiproliferative activity using the MTT assay against five human cancer cell lines, namely, A549, HCT116, PC3, HT29, and MCF-7 in parallel with the non-cancerous human lung cell line WI-38. The results showed that 3e and 3f have potential cytotoxic activities, especially on A549 cells with IC50 = 2.3 µM and 1.15 µM, respectively. Meanwhile, they recorded a minimal cytotoxic effect on WI-38 cells. Concerning the molecular mechanism of action, the present study showed the inhibitory effect of the six compounds against total EGFR. The most potent EGFR inhibitors were 3e and 3f with IC50 = 0.031 µM and 0.023 µM, respectively. The selectivity index of 3f for EGFRT790M was 1.81 times more selective than that of lapatinib. In addition, 3e and 3f initiated cell cycle arrest at the G2/M and pre-G1 phases along with the downregulation of anti-apoptotic protein Bcl2 and the upregulation of pro-apoptotic proteins: p53, Bax, and caspases 3, 8, and 9. Further studies are recommended to evaluate animal models’ promising anticancer activity and molecular mechanism of triazolo[3,4-a]isoquinoline derivatives 3e and 3f.

Preclinical characterization of XB002, an anti-tissue factor antibody-drug conjugate for the treatment of solid tumors.

Tissue factor (TF) is overexpressed in various cancers, where its expression is generally associated with poor disease outcomes. XB002 is an anti-TF antibody-drug conjugate designed to deliver a cytotoxic payload to TF-expressing tumors while minimizing adverse events related to disruption of TF function, notably bleeding. XB002 is composed of a zovodotin linker-payload conjugated to a monoclonal antibody (clone 25A3) that binds to TF with high affinity (KD = 0.86 nM). In vitro coagulation studies indicated that 25A3 did not interfere with the clotting cascade; at a 100 nM concentration, 25A3 had no effect on activation of coagulation factor X or thrombin generation. XB002 was internalized in TF-expressing cancer cell lines and displayed potent cytotoxic activity at sub-nanomolar concentrations. When evaluated in the HPAF-II xenograft model, XB002 (1.5 mg/kg, IV) given once weekly for 2 weeks induced complete regression with no tumor growth even at 5 weeks after the second dose. In murine patient-derived xenograft models, a single dose of XB002 (10 mg/kg, IV) inhibited tumor growth across multiple cancer models including bladder, cervical, gastric, head and neck squamous cell carcinoma (HNSCC), and non-small cell lung cancer. Further, complete tumor regression was observed in both the cervical and HNSCC models by 30 days post-treatment. In non-human primate models, XB002 showed exposure in the desired range and no evidence of bleeding or neutropenia. Taken together, these data demonstrate potential anti-tumor activity across a spectrum of oncology indications and strongly support its clinical development.

Effective Synthesis of C20-Epi-Isothiocyanato-Salinomycin and its Thiourea Derivatives as Potential Anticancer Agents.

Salinomycin, a naturally occurring polyether ionophore antibiotic isolated from Streptomyces albus, has been demonstrated potent cytotoxic activity against a variety of cancer cell lines. In particular, it exhibits selective targeting of cancer stem cells. However, systemic toxicity, drug resistance and low bioavailability of the drug significantly limit its potential applications. In this study, the C20-epi-isothiocyanate of salinomycin was designed and synthesized, and then reacted with amines as a versatile synthon to assemble a series of salinomycin thiourea derivatives, which improved the druggability of salinomycin. The antiproliferative activities of the compounds were evaluated in vitro against A549, HepG2, HeLa, 4T1, and MCF-7 cancer cell lines using the CCK-8 assay. The pharmacological results showed that some salinomycin thiourea derivatives exhibited excellent inhibitory activity against at least one of the tested tumor cells and high selectivity. Further mechanistic studies showed that compound 9 f, containing a 3,5-difluorobenzyl moiety, could directly induce apoptosis, probably by increasing caspase-9 protein expression and cell cycle arrest in G1 phase in a concentration dependent manner.

5-methyl-N'-(thiophen-2-ylmethylene)-1H-pyrazole-3-carbohydrazide as potent anticancer agent: Synthesis, spectroscopic characterization, anticancer activity and DFT studies

A new pyrazole-hydrazide hydrazone derivative, named 5-methyl-N'-(thiophen-2-ylmethylene)-1H-pyrazole-3-carbohydrazide (TMPC) has been synthesized and characterized by FT-IR, UV–Vis, 1H NMR, 13C NMR, and HRMS-ESI. Its cytotoxic activity was tested on various cancer and healthy cell lines using the XTT method. In addition, the advanced anticancer mechanism was investigated by flow cytometry analysis. Hybrid B3LYP/6–311++G** calculations reveal two stable C1 and C2 conformers of TMPC with energy differences of 28.96 kJ/mol in the gas phase and 8.50 kJ/mol in ethanol solution. Comparisons among the experimental NMR, UV and infrared spectra with the predicted ones support the presence of both forms in solution. The presence of dimer C2 justify the intensities and numerous bands observed in the IR spectrum in the 2000–10 cm−1 region. Probably, the repulsion between the N7 and O1 atoms in C1 explain its lower stability and the higher solvation energy (-108.20 kJ/mol) observed for this form in ethanol than C2 (-88.01 kJ/mol). NBO calculations suggest that both forms are stable in the two media while the AIM analyses evidence the higher stability of C2 than C1 due to the N9-H22···N7 interaction observed only for this conformer in the gas phase. Gap values suggest high reactivities of both forms, as compared with similar pyrazole-carbohydrazide species. Full vibrational assignments are reported for both forms of TMPC together with the main scaled force constants. The XTT results showed that TMPC exhibited a selective cytotoxic effect on the tested cancer cell lines in a dose- and time-dependent manner, and also displayed the most potent cytotoxic activity against breast cancer MCF-7 cells with an IC50 value of 22.79 µM after 48 h Flow cytometric analyses showed that TMPC induced apoptosis and suppressed PI3K/Akt signaling in MCF-7 cells.

Shikonin Stimulates Mitochondria-Mediated Apoptosis by Enhancing Intracellular Reactive Oxygen Species Production and DNA Damage in Oral Cancer Cells.

Phytotherapy has rendered a new insight towards the treatment of various cancers, including oral cancer with fewer side effects, over the traditional chemotherapeutic drugs to overcome chemoresistance. Shikonin (Shk) is a natural biologically active alkaloid found in the Lithospermum erythrorhizon plant's root. It has potent cytotoxic activities against various cancers. Our study revealed the release time and anticancer potential of Shk on the SCC9 and H357 oral cancer cell lines. We investigated the antiproliferative, antimigratory, cell cycle arresting and apoptosis promoting activity of Shk in oral cancer cells by performing MTT and morphological assay, colony, and tumor sphere formation assay, AO/EtBr and DAPI staining, Annexin V-FITC/PI staining, assay for reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) measurement, comet assay, qRT-PCR, and western blot analysis. We also checked the interaction of DNA and Shk by docking and CD spectroscopy and EtBr displacement assay. As a result, we found that Shk reduced the viability, proliferation, and tumorigenicity of SCC9 and H357 cells in a time and concentration-dependent manner. We obtained half-maximal inhibitory concentration (IC50) at 0.5 µM for SCC9 and 1.25 µM for H357. It promotes apoptosis via overexpressing proapoptotic Bax and caspase 3 via enhancing ROS that leads to MMP depletion and DNA damage and arrests cells at the G2/M & G2/S phase. The antimigratory activity of Shk was performed by analyzing the expression of markers of epithelial-mesenchymal transition like E-cadherin, ZO-1, N-cadherin, and vimentin. These overall results recommended that Shk shows potent anticancer activity against oral cancer cell lines in both in vitro and ex vivo conditions. So, it could be an excellent agent for the treatment of oral cancer.

Green approach of cobalt sulfide nanoparticles from novel red stigma of Crocus sativus and multifaceted biomedical advancement

The present study was based on green protocols for synthesizing cobalt sulfide nanoparticles using saffron stigma flower extract (Crocus sativus), as saffron is considered a potent traditional medicine. Furthermore, the novel cobalt sulfide (CoS) nanoparticles prepared by the green approach for the first time with saffron improved showed cytotoxicity and antibacterial activity, as well as significant antitumor activity of Hela, A549, and MCF 7 cells viz in vitro studies. The saffron-cobalt sulfide nanoparticles underwent characterization using various techniques which include the X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Advances in scanning electron microscopy (SEM), and high-resolution transmission electron microscopy (HR-TEM), and the energy dispersive X-ray analysis spectroscopy. Both XRD, and FTIR confirmed the synthesis of pure cobalt sulfide nanoparticles. The resulting saffron-based cobalt sulfide nanoparticles exhibited a nanosphere structure, as confirmed by HRTEM, indicating the formation of nanosphere and microstructures. In vitro studies were conducted to assess the cytotoxicity and cell viability of Hela cells, A549, and MCF-7 cells. And, antibacterial studies were performed against various bacterial strains using different concentrations of cobalt sulfide nanoparticles derived from the red stigma of saffron (Crocus sativus) only the red stigma extract. The MTT assay analysis, cell viability, and morphological studies demonstrated the cytotoxic studies of the synthesized cobalt sulfide nanoparticles on cancer cells. The antibacterial test of the nanoparticles was also evaluated, revealing significant zones of inhibition (mm) against pathogens and cobalt sulfide nanoparticles using saffron extract, showcasing their potent cytotoxic, antibacterial, and antitumor activities with promising biomedical applications.

Engineered Porous Beta-Cyclodextrin-Loaded Raloxifene Framework with Potential Anticancer Activity: Physicochemical Characterization, Drug Release, and Cytotoxicity Studies.

Cancer ranks as the second most common cause of mortality as depicted by the World Health Organization, with one in six deaths being cancer-related mortality. Taking the lead in females, breast cancer is the most common neoplasm. Raloxifene, a selective estrogen receptor modulator, has been utilized as a chemotherapeutic agent for the treatment of breast cancer in postmenopausal women. However, its poor aqueous solubility hinders its clinical applications. Beta-cyclodextrin-based framework is a novel class of nano-vectors that used to potentiate the solubility and dissolution rate of poorly soluble drugs. The present study investigates the solubility and dissolution rate enhancement as well as the potential cytotoxic activity of raloxifene-loaded nanosponges formulation. The fabrication and optimization of cyclodextrin nanosponges crosslinked with diphenyl carbonate was portrayed through stoichiometric selection of cyclodextrin-to-crosslinker ratio. The complexation phenomenon and nanosponges formation were validated using FTIR, PXRD, TEM, and SEM examination. Raloxifene-loaded nanosponges exhibited a 440±8.5 nm particle size, a negative zeta potential of 25.18±2.3 mV and a partial drug incorporation. Moreover, the drug loaded nanosponges demonstrated an in-vitro significantly enhanced dissolution behavior. Furthermore, the in-vitro cytotoxicity of the raloxifene-loaded nanosponges on MCF-7 breast cancer cell lines was statistically significant compared to the complex-free raloxifene. The cytotoxic behavior provided evidence that the incorporation of raloxifene within the nanosponges structure enhanced its anticancer activity and represents a potential nanocarrier for anticancer agent delivery.

Uncovering the therapeutic potential of green pea waste in breast cancer: a multi-target approach utilizing LC-MS/MS metabolomics, molecular networking, and network pharmacology

Background Pisum sativum(PS) is a universal legume plant utilized for both human and animal consumption, particularly its seeds, known as green peas. The processing of PS in food industries and households produces a significant amount of waste that needs to be valorized.MethodsIn this study, the metabolite profiles of the 70% ethanolic extracts of PS wastes, namely peels (PSP) and a combination of leaves and stems (PSLS), were investigated by liquid chromatography-electrospray ionization-quadrupole time-of-flight tandem mass spectrometry (LC-ESI-QTOF-MS/MS) followed by molecular networking.ResultsDifferent classes of metabolites were identified, being flavonoids and their derivatives, along with phenolic acids, the most abundant categories. Additionally, a comprehensive network pharmacology strategy was applied to elucidate potentially active metabolites, key targets, and the pathways involved in cytotoxic activity against breast cancer. This cytotoxic activity was investigated in MCF-7 and MCF-10a cell lines. Results revealed that PSLS extract exhibited a potent cytotoxic activity with a good selectivity index (IC50 = 17.67 and selectivity index of 3.51), compared to the reference drug doxorubicin (IC50 = 2.69 µg/mL and selectivity index of 5.28). Whereas PSP extract appeared to be less potent and selective (IC50 = 32.92 µg/mL and selectivity index of 1.62). A similar performance was also observed for several polyphenolics isolated from the PSLS extract, including methyl cis p-coumarate, trans p-coumaric acid, and liquiritigenin/ 7-methyl liquiritigenin mixture. Methyl cis p-coumarate showed the most potent cytotoxic activity against MCF-7 cell line and the highest selectivity (IC50 = 1.18 µg/mL (6.91 µM) and selectivity index of 27.42). The network pharmacology study revealed that the isolated compounds could interact with several breast cancer-associated protein targets including carbonic anhydrases 1, 2, 4, 9, and 12, as well as aldo-keto reductase family 1 member B1, adenosine A3 receptor, protein tyrosine phosphatase non-receptor type 1, and estrogen receptor 2.ConclusionThe uncovered therapeutic potential of PSLS and its metabolite constituents pave the way for an efficient and mindful PS waste valorization, calling for further in-vitro and in-vivo research.Graphical

Computational metal-flavonoids complexes presentation of greenly synthesized silver nanoparticles combined flavonoids from Lens culinaris L. as anticancer agents using BcL-2 and IspC proteins

Lens culinaris L., has been widely recognized for its medical applications. LC-ESI-TOF-MS identified 22 secondary metabolites including phenolics, flavonoids, and anthocyanidin glycosides among its total extract (LCTE). The study aimed to apply LCTE as a biogenic material for reducing and capping the silver nanoparticles (LC-AgNPs). The ynthesized LC-AgNPs were characterized using different techniques. The UV absorption was observed at λ max 379 nm. LC-AgNPs were spherical, with 19.22 nm average size. The face cubic centre nature was demonstrated by HR-TEM and XRD. The LC-AgNPs were then evaluated for their anticancer and antimicrobial potentials. LC-AgNPs showed an extremely potent cytotoxic activity against MCF-7, HCT-116 and HepG2 cell lines (IC50= 0.37, 0.35 and 0.1 µg/mL, respectively). LC-AgNPs induced significant apoptotic effects in the three examined cancer cell lines. LC-AgNPs resulted in sequestration of cells in G1 phase of the cell cycle in both MCF-7 and HCT-116 cells, meanwhile it trapped cells at the G2 phase in HepG2 cells. Moreover, the antimicrobial activity of LC-AgNPs was highly confirmed against Klebsiella pneumoniae and Acinetobacter baumannii. Molecular docking study designated Kaempferol-3-O-robinoside-7-O-rhamnoside and Quercetin-3-D-xyloside as the topmost LCTE active constituents that caused inhibition of both Bcl-2 and IspC cancer targets in combination with the produced silver nanoparticles.

Synthesis, characterization, and cytotoxicity studies of diimine derivatives and their ruthenium(II)-p-cymene complexes

The reaction of five di-imines obtained by condensation of etilendiamine with 4-hydroxybenzaldehyde (L1), 2,4-dihydroxibenzaldehyde (L2) and 1-(2,4-dihydroxyphenyl)ethan-1-one (L3) or, condensations of glyoxal with 4-aminophenol (L4) and 4-amino-3-fluorphenol (L5) with [Ru2(Cl)4(η6-p-cymene)2] was studied. In absence of silver salts, four cationic complexes of formula [RuCl(η6-p-cymene)(Ln)]X where n = 1, 3, 4 and X = Cl and, n = 5 and X = PF6 could be isolated as pure solid materials. The complexes were characterized by different spectroscopic techniques and the X-ray structures of the L1 hydrate and its complex [RuCl(η6-p-cymene)(L1)]Cl were also determined. These studies confirm the N,N’-bidentate nature of the ligand L1 and the pseudo-octahedral geometry of the ruthenium coordination environment in the complex. Furthermore, the complex derived from L3, shows a potent cytotoxic activity against tumor cell line A549.

New sesquiterpenes from the soft coral Litophyton arboreum.

Two new sesquiterpenes; 8α,11-dihydroxy-β-cyperon (2), and 5-epi-7α-hydroxy-( +)-oplopanone (3), were isolated from the soft coral Litophyton arboreum, together with nine known ones, including five sesquiterpenes; 11-hydroxy-8-oxo-β-cyperon (1), alismoxide (4), 5β,8β-epidioxy-11-hydroxy-6-eudesmene (5), chabrolidione B (6), 7-oxo-tri-nor-eudesm-5-en-4β-ol (7), two sterols; 7β-acetoxy-24-methyl-cholesta-5,24(28)-diene-3β,19-diol (8), nebrosteroid M (9), and two glycerol derivatives; chimyl alcohol (10) and batyl alcohol (11). The structures of the isolated compounds were characterized using spectroscopic techniques, predominately HR-ESI-MS, 1D, 2D-NMR, and ECD analyses. Compounds 1-11 were evaluated for their cytotoxic activity against three human cancer-cell lines (A549, MCF-7 and HepG2), and anti-leishmanial potential against the causal parasite, Leishmania major. Compounds 4, 8, and 9 exhibited potent cytotoxic activity against the A549 cell line (IC50 = 17.0 ± 2.5, 13.5 ± 2.1, and 16.5 ± 1.3μg/ml, respectively) as compared with the standard antitumor agent etoposide (IC50 28.4 ± 4.5μg/ml). In addition, compound 9 exhibited remarkable cytotoxic activity against MCF-7 cell line (IC50 = 24.7 ± 2.1μg/ml: 22.2 ± 4.2μg/mL for etoposide).

Diversity Oriented Strategy (DOS) for the Efficient Synthesis of Benzofuro[2,3-b]pyridine Derivatives with Anticancer Activity.

Benzofuropyridines (BFP) are polycyclic compounds with known applications in neuronal diseases. However, its derivatization patterns and anticancer potential remains unexplored. Leveraging the idea of diversity-oriented synthesis (DOS), we developed a highly efficient synthetic route for BFP to increase the library of available analogs producing three compounds in one reaction set up, including the 2O-, 6O-, and the 1N-substituted species, also producing the unusual 2-pyridone derivatives. Key bromination reaction of the BFP moiety was successfully described which can widen the available variation in the compounds' structure. The cytotoxic activity of the compounds was assessed against SH-SY5Y (neuroblastoma), HepG2 (hepatocellular carcinoma), Kb (human oral epidermoid), HeLa (cervical) and MCF-7 (breast) cancer cell lines. In the series, the m-bromobenzyl (5b), methylcyano (5g) and propargyl (5h) 2O-derivatives demonstrated good selectivity against cancer cells with selectivity index (SI) of >71 for 5g against HeLa over the normal cells, as compared to the standard drug, Doxorubicin (SI = 6.7). The quantitative structure-activity relationship (QSAR) analysis revealed an impressive correlation of the defined descriptors with the bioactivity having an R2 value of 0.971 and 0.893 for Kb and HeLa respectively. Altogether, our work highlighted new information on the synthesis of BFP derivatives with potent cytotoxic activity.

Iriomoteolide-1a and -1b: Structure Elucidation by Integrating NMR Spectroscopic Analysis, Theoretical Calculation, and Total Synthesis.

The structure of iriomoteolide-1a, a marine macrolide with potent cytotoxic activity against human cancer cells, has been under scrutiny for more than a decade since the first total synthesis of the proposed structure was achieved by Horne. Here we disclose the correct structure of iriomoteolide-1a. Given a huge number of possible stereoisomers, we adopted an integrated strategy toward the structure elucidation of iriomoteolide-1a: (1) NMR spectroscopic analysis/molecular mechanics-based conformational analysis for configurational reassignment of the macrolactone domain; (2) model synthesis for validating the reassigned configuration of the macrolactone domain; (3) GIAO NMR calculation/DP4+ analysis of side chain stereoisomers; and (4) total synthesis of the most likely structure. Moreover, the correct structure of iriomoteolide-1b, a natural congener, was also determined by an integration of NMR spectroscopic analysis, GIAO NMR calculation/DP4+ analysis, and total synthesis.