In-vitro and in silco analysis and antitumor studies of novel Cu(II) and V(V) complexes of N-p-Tolylbenzohydroxamic acid.

Copper(L2Cu) and vanadium(L2VOCl) complexes of N-p-tolylbenzohydroxamic acid (LH) ligand have been investigated for DNA binding efficacy by multiple analytical, spectral, and computational techniques. The results revealed that complexes as groove binders as evidenced by UV absorption. Fluorescence studies including displacement assay using classical intercalator ethidium bromide as fluorescent probe also confirmed as groove binders. The viscometric analysis too supports the inferences as strong groove binders for both the complexes. Molecular docking too exposed DNA as a target to the complexes which precisely binds L2Cu, in the minor groove region while L2VOCl in major groove region. Molecular dynamic simulation performed on L2Cu complex revealing the interaction of complex with DNA within 20 ns time. The complex stacked into the nitrogen bases of oligonucleotides and the bonding features were intrinsically preserved for longer simulation times. In-vitro cytotoxicity study was undertaken employing MTT assay against the breast cancer cell line (MCF-7). Potential cytotoxic activities were observed for L2Cu and L2VOCl complexes with IC50 values of showing 71 % and 74 % of inhibition respectively.

Phytochemical characterization by GC-MS and in vitro evaluation of antiproliferative and antimigratory studies of Leucas aspera leaf extracts on MDA-MB-231 cell line.

Breast cancer is the most recurrently identified and one of women's prominent causes of death. Currently, researchers have turned their focus on natural chemicals from synthetic chemicals due to their environmental, economic, and health benefits. Considering this, the medicinal plant Leucas aspera was chosen for the current study. The aim of this study was to isolate and characterize secondary metabolites from L. aspera and determine the antiproliferative and antimigratory activities in the MDA-MB-231 cell line under in vitro conditions. Phytochemicals from L. aspera were isolated through sequential extraction using hexane, dichloromethane, and ethyl acetate. These extracts were qualitatively screened, subjected to FT-IR, and analyzed using GC-MS. The antiproliferative activity was determined through the MTT assay. Scratch assay was utilized to determine the antimigratory activity of the plant extracts. The phytochemical analysis revealed the presence of steroids, alkaloids, phenols, flavonoids, galactose, tannins, saponins, and amino acids in the extracts. The results of the cell viability assay indicated that the crude dichloromethane and ethyl acetate extracts inhibited cell proliferation, with inhibitory concentrations of 5 and 3 µg/ml, respectively. In contrast, the crude hexane extract did not exhibit any cytotoxicity. Furthermore, the scratch assay results showed that the plant extracts had cell migration inhibitory properties. The outcomes of the current study conclude that L. aspera possesses active therapeutic agents with strong anticancer potential, effectively impeding the proliferation and invasion of MDA-MB-231. Further studies are needed to identify the potential active agents that contribute to these activities.

Rosellichalasins A-H, cytotoxic cytochalasans from the endophytic fungus Rosellinia sp. Glinf021.

Eight new cytochalasans rosellichalasins A-H (1-8), as well as two new shunt metabolites rosellinins A (9) and B (10) before intramolecular Diels-Alder cycloaddition reaction in cytochalasan biosynthesis, along with nine known cytochalsans (11-19) were isolated from the endophytic fungus Rosellinia sp. Glinf021, which was derived from the medicinal plant Glycyrrhiza inflata. Their structures were characterized by extensive analysis of 1D and 2D NMR as well as HRESIMS spectra and quantum chemical ECD calculations. The cytotoxic activities of these compounds were evaluated against four human cancer cell lines including HCT116, MDA-MB-231, BGC823, and PANC-1 with IC50 values ranging from 0.5 to 58.2 µM.

New Solasodine-type Glycoalkaloids Isolated from Solanum nigrum and Their Cytotoxic Activity.

Three undescribed solalodine-type glycoalkaloids, named  solanigrinoside A-C (1-3), and six known compounds (4-9) were isolated from the whole plants of Solanum nigrum. Their structures were elucidated based on analysis of HR-ESI-MS, 1D- and 2D-NMR spectral data, and comparison with those reported in literatures. The solanigrinoside A-C (1-3), solasodine (4), and 3-acetoxysolasodine (5) exhibited cytotoxic effects against LU-1, Hep-G2, and MCF-7 cells with IC50 values in range from 4.6 µM to 56.2 µM. Compound 2 showed the significant cytotoxic activity with corresponding IC50 values of 5.7 µM, 7.9 µM, and 4.6 µM, respectively.

Design, synthesis, insilco study and biological evaluation of new isatin-sulfonamide derivatives by using mono amide linker as possible as histone deacetylase inhibitors.

OBJECTIVE: Aim: To evaluate the cytotoxic activity of newly synthesized a series of novel HDAC inhibitors comprising sulfonamide as zinc binding group and Isatin derivatives as cap group joined by mono amide linker as required to act as HDAC inhibitors. PATIENTS AND METHODS: Materials and Methods: The utilization of sulfonamide as zinc binding group joined by N-alkylation reaction with ethyl-bromo hexanoate as linker group that joined by amide reaction with Isatin derivatives as cap groups which known to possess antitumor activity in the designed of new histone deacetylase inhibitors and using the docking and MTT assay to evaluate the compounds. RESULTS: Results: Four compounds have been synthesized and characterized successfully by ART-FTIR, NMR and ESI-Ms. the compounds were synthesized and characterized by successfully by ART-FTIR, NMR and ESI- Ms. Assessed for their cytotoxic activity against human colon adenocarcinoma MCF-7 (IC50, I=105.15, II=60.00, III=54.11, IV=56.57, vorinostat=28.41) and hepatoblastoma HepG2 (IC50, I=63.91, II=135.18, III=118.85, IV=51.46, vorinostat=37.50). Most of them exhibited potent HDAC inhibitory activity and significant cytotoxicity. CONCLUSION: Conclusions: The synthesized compounds (I, II, III and IV) showed cytotoxicity toward MCF-7 and HepG2 cancer cell lines and their docking analysis provided a preliminary indication that they are viable [HDAC6] candidates.

Determination of chemical components of the endemic species Allium turcicum L. plant extract by LC-MS/MS and evaluation of medicinal potentials.

The Allium turcicum L. (Zuzubak) plant as a cultivated vegetable have various health benefits and consumed as a food. Due to the shortcoming evidence in literature and the importance of this plant in folk medicine, in the present study, for the first time, we evaluated the bioactive profile of components (using LC-MS/MS), cytotoxicity, anticancer, antioxidant, and antibacterial prospectives of Zuzubak methanol extract. Reported results show that the extract is rich in bioactive compounds and has anticancer activity with breast cancer cells (MCF-7), human prostate cancer cells (DU-145), and Human osteosarcoma cancer Cell lines of (IC50) in dose dependent manner in the concentration range of 31.25 µg/mL and 2000 µg/mL for 24 and 48 h. Western blotting results determined that the extract significantly suppressed the growth of U2OS, MCF-7, and DU-145 cancer cells by down expression of Ang-1 (angiogenic protein) and Beclin-1 (autophagy protein) and overexpression of Bax (a proapoptotic protein). The oxidative stress indices showed a reduction in RPE-1 and MCF-7 cells and an upsurge in U2OS and DU-145 cells. Additionally, the antimicrobial assay showed suppression of the growth of various pathogenic microorganisms in 4.00-8.00 µg/concentrations of Zuzubak extract using the microdilution method. The phytochemicals identified showed promising anticancer, antioxidant effects, and antimicrobial properties, representing a valuable herbal source for drug development studies.

Hericium VN, an undescribed compound isolated from Hericium erinaceus and its cytotoxic activity on human brain astrocytoma.

Hericium erinaceus is a species of mushroom with high nutritional value that is used mainly as food in tropical countries. Phytochemical study of H. erinaceus led to the isolation of an undescribed compound, named as hericium VN (1), together with nine known compounds, 1-(2-formyl-1-pyrrolyl)butanoic acid (2), herierin III (3), 5'-(methylthio)adenosine (4), adenosine (5), nicotinic acid (6), (22E,24R)-5α,8α-epidioxyergosta-6,9(11),22-trien-3ß-ol (7), 5α,8α-peroxycerevisterol (8), (22E,24R)-5α,8α-epidioxy-egosta-6,22-diene 3-O-ß-D-glucopyranoside (9), and cerevisterol (10) based on extensive analyses of HR-ESI-MS, 1D and 2D NMR spectra. The absolute configuration of compound 1 was determined by experimental combined with calculated electronic circular dichroism spectra. Compound 7 exhibited cytotoxic effects against brain tumor cell line CCF-STTG1 with the IC50 value of 15.50 µM, compared to that of the positive control compound, doxorubicin, which showed IC50 value of 15.84 µM.

Synthesis and cytotoxic evaluation of glycosyl derivatives of icaritin.

A series of glycosyl alkyl/triazol-linked icaritin derivatives have been designed and synthesised. The target glycosyl derivatives were evaluated for their anticancer activity against three human cancer cell lines. The results of preliminary anticancer tests in vitro revealed that mannose derivatives 10a-10c (100 µM) with different aliphatic chain lengths exhibited increased cytotoxicity against HepG2 and SK-OV-3 cells compared with the parent compound icaritin. The data indicated that the kind of glycosyl groups and linkers affected the anticancer potency significantly. The ADME analysis of derivatives 10a-10c was also performed.

Two new triterpenoid saponins and two new goodyerosides isolated from the whole plant of Tournefortia sibirica.

Two new triterpenoid saponins (oleanolic acid 2ß-hydroxyl-3-O-ß-D-glucuronopyranoside-6'-O-buthyl ester (1) and oleanolic acid 2ß-hydroxyl-3-O-[ß-D-glucuronopyranosyl-6'-O-methylester]-28-O-ß-D-glucopyranoside (2)) and two new goodyerosides (4-methylenefuran-2(5H)-one (6'-O-vanilloyl)-ß-D-glucopyranoside (3), 3-hydroxy-2(5H)-furanone, 4-(6'-O-vanilloyl)-ß-D-glucopyranoside (4)), together with seven known compounds (5-11) were isolated from the whole plant of Tournefortia sibirica L. The chemical structures of the compounds were determined by spectroscopic analysis (1D and 2D NMR) and HR-ESI-MS. Compounds 1, 6 and 9 showed significant cytotoxicity towards A549, SK-Hep1 and HeLa cells, with IC50 values ranging from 1.68 ± 0.09 to 6.87 ± 0.13 µM.

Five undescribed cyclopeptides from Cordyceps militaris.

Ustiloxins I-M (1-5), five undescribed cyclopeptides bearing a 15-membered macrocyclic skeleton, were isolated from Cordyceps militaris. The structures of 1 and 5 were identified by spectroscopic and crystallographic methods, whereas the structures of 2-4 were assigned by spectroscopic and computational approaches. Biological evaluation of all the compounds toward human triple-negative breast cancer cells revealed that compounds 4 and 5 are toxic with IC50 values of 64.29 µM and 28.89 µM, respectively.

Toonanoronoids A-E, five new limonoids from Toona ciliata var. yunnanensis.

Five new B-seco-limonoids, namely toonanoronoids A-E (1-5), in conjunction with three previously reported compounds, were isolated from the EtOAc extract of the twigs and leaves of Toona ciliata var. yunnanensis. Their structures were elucidated through comprehensive spectroscopic and X-ray crystallographic analysis. The cytotoxic activities of new compounds against five human tumor cell lines (HL-60, SMMC-7721, A549, MCF-7, and SW480) were screened, Compounds 4 and 5 exerted inhibition toward two tumor cell lines (HL-60, SW-480) with IC50 values between 1.7 and 5.9 µM.

A new triterpenoid saponin and a new natural saponin from the roots of Bupleurum scorzonerifolium willd.

Sixteen triterpenoid saponins were isolated from the roots of Bupleurum scorzonerifolium Willd., including a new triterpenoid saponin and new natural saponin that was characterised by NMR for the first time, along with 14 known triterpenoid saponins. The structures of the compounds were established by 1D and 2D NMR spectroscopy, HR-ESI-MS, and comparison with the literature. The cytotoxic activity of the compounds against 4T1 cells was determined using the CCK8 method. Compounds 9 and 6 showed the strongest cytotoxic activity with IC50 values of 2.75 ± 0.86 and 3.78 ± 0.50 µM, respectively. Compounds 2-5 and 8 showed potent cytotoxic activity. Compounds 14 and 16 showed moderate cytotoxicity.

10-Secocycloartane (=9,19-cyclo-9,10-secolanostane) triterpenoid saponins: Huangqiyenins M-X from Astragalus membranaceus (Fisch.) Bge.

Phytochemical investigations of the leaves of Astragalus membranaceus (Fisch.) Bge. have led to the isolation of 12 undescribed triterpenoid saponins named huangqiyenins M-X. The structures of the undescribed compounds were determined using NMR and HRESIMS data. The cytotoxicity of these compounds against the RKO and HT-29 colon cancer cell lines was evaluated. Among these compounds, huangqiyenin W exhibited the highest cytotoxic activity against RKO colon cancer cells, whereas huangqiyenin Q and W showed moderate cytotoxic activity against HT-29 colon cancer cells. The network pharmacology results indicated that STAT3, IL-2 and CXCR1 are the correlated targets of huangqiyenin W against colon cancer, with AGE-RAGE and Th17 cell differentiation as the key signaling pathways.

Isolation, Identification and Chemical Modification of Bufadienolides from Bufo melanostictus Schneider and Their Cytotoxic Activities against Prostate Cancer Cells.

The traditional Chinese medicine toad venom (Venenum bufonis) has been extensively used to treat various diseases, including cancers, in China and other Southeast Asian countries. The major constituents of toad venom, e.g., bufadienolides and alkaloids, exhibit broad-spectrum pharmacological effects in cancers. Herein, two new bufadienolides (1 and 2), along with eleven known compounds (3-13) were successfully isolated from Bufo melanostictus Schneider. Their structures were elucidated by extensive spectroscopic data and X-ray diffraction analysis. Furthermore, four lactam derivatives were synthesized through the transformation of bufadienolides lactones. The inhibitory effects of these compounds against human prostate cancer cell lines PC-3 and DU145 were evaluated. The outcomes indicated a notable trend, with a substantial subset displaying nanomolar range IC50 values against PC-3 and DU145 cells, underscoring their pronounced cytotoxicity. Moreover, a noteworthy distinction surfaces, wherein lactones consistently outperformed their lactam counterparts, further validating their heightened potency for the treatment of prostate cancer. This study contributes significant preclinical evidence substantiating the therapeutic viability of bufadienolides and toad venom as intervention strategies for prostate cancer.

Genome-guided discovery of two undescribed 6,6-spiroketal polyketides and stereochemical correction of bafilomycins P and Q from the marine-derived Streptomyces sp. SCSIO 66814.

Bafilomycins are macrocyclic polyketides with intriguing structures and therapeutic value. Genomic analysis of Streptomyces sp. SCSIO 66814 revealed a type I polyketide synthase biosynthetic gene cluster (BGC), namely blm, which encoded bafilomycins and featured rich post-modification genes. The One strain many compounds (OSMAC) strategy led to the discovery of six compounds related to the blm BGC from the strain, including two previously undescribed 6,6-spiroketal polyketides, streptospirodienoic acids D (1) and E (2), and four known bafilomycins, bafilomycins P (3), Q (4), D (5), and G (6). The structures of 1 and 2 were determined by extensive spectroscopic analysis, quantum calculation, and biosynthetic analysis. Additionally, the absolute configurations of the 6/5/5 tricyclic ring moiety containing six consecutive chiral carbons in the putative structures of 3 and 4 were corrected through NOE analysis, DP4+ calculation, and single-crystal X-ray diffraction data. Bioinformatic analysis uncovered a plausible biosynthetic pathway for compounds 1-6, indicating that both streptospirodienoic acids and bafilomycins were derived from the same blm BGC. Additionally, sequence analysis revealed that the KR domains of module 2 from blm BGC was B1-type, further supporting the configurations of 1-4. Notably, compounds 3 and 4 displayed significant cytotoxic activities against A-549 human non-small cell lung cancer cells and HCT-116 human colon cancer cells.

Secondary metabolites and their bioactivities from Paecilomyces gunnii YMF1.00003.

Four new polyketides (1-4) and seven known compounds (5-11) including three polyketides and four sterols were isolated from the fermented extracts of Paecilomyces gunnii YMF1.00003. The new chemical structures were determined through the analysis of the nuclear magnetic resonance and high-resolution electrospray ionization mass spectrometry, and their configurations were subsequently confirmed by nuclear overhauser effect spectroscopy, the calculated electronic circular dichroism (ECD) spectra, and quantum chemical calculations of the NMR data (qcc NMR). Based on the results of pre-activity screening and compound structure target prediction, certain metabolites were assayed to evaluate their cytotoxic and protein kinase Cα inhibitory activities. Results indicated that 3ß-hydroxy-7α-methoxy-5α,6α-epoxy-8(14),22E-dien-ergosta (8) exhibited potent cytotoxic activity, with half-maximal inhibitory concentration values of 3.00 ± 0.27 to 15.69 ± 0.61 µM against five tumor cells, respectively. The new compound gunniiol A (1) showed weak cytotoxic activity at a concentration of 40 µM. At a concentration of 20 µg/mL, compounds 1, 6, and 7 exhibited protein kinase Cα inhibition by 43.63, 40.93, and 57.66%, respectively. This study is the first to report steroids demonstrating good cytotoxicity and polyketides exhibiting inhibitory activity against protein kinase Cα from the extracts of P. gunnii.

Synthesis of a New Series of Anthraquinone-Linked Cyclopentanone Derivatives: Investigating the Antioxidant, Antibacterial, Cytotoxic and Tyrosinase Inhibitory Activities of the Mushroom Tyrosinase Enzyme Using Molecular Docking.

Purpose: New bioactive anthraquinone derivatives are investigated for antibacterial, tyrosinase inhibitory, antioxidant cytotoxic activity, and molecular docking. Methods: The compounds were produced using the grindstone method, yielding 69 to 89%. These compounds were analyzed using IR, 1H, and 13C NMR and elemental and mass spectral methods. Additionally, the antibacterial, antioxidant, and tyrosinase inhibitory activities of all the synthesised compounds were evaluated. Results: Compound 2 showed remarkable tyrosinase inhibition activity, with an (IC50: 13.45 µg/mL), compared to kojic acid (IC50: 19.40 µg/mL). It also exhibited moderate antioxidant and antibacterial activities with respect to the references BHT and ampicillin, respectively. Kinetic analysis revealed that the tyrosinase inhibitory activity of compound 2 was non-competitive and competitive, whereas that of compound 1 was low. All compounds (1-8) were significantly less active than doxorubicin (LC50: 0.74±0.01µg/mL). However, compound 2 affinity for the 2Y9X protein was lower than kojic acid, with a lower docking score (-8.6 kcal/mol compared to (-4.7 kcal/mol), making it more effective. Conclusion: All synthesized compounds displayed remarkable antibacterial, tyrosinase inhibitory, antioxidant, and cytotoxic activities, with compound 2 showing exceptional potency as a multitarget agent. Anthraquinone substituent groups may offer the potential for the development of treatments. The derivatives were synthesized using the grindstone method, and their antibacterial, antioxidant, tyrosinase inhibitory, and cytotoxic activities were inspected. Molecular docking and molecular dynamics simulations were performed using compound 2 and kojic acid to validate the results and confirm the stability of the compounds.

Siamfuranones A-C, three novel furanone derivatives from the flowers of Uvaria siamensis and their biological activities.

Three previously undescribed furanone derivatives named siamfuranones A-C (1-3), together with 11 known compounds (4-14), were isolated from the flowers of Uvaria siamensis. Their planar structures were determined through analysis of spectrometric and spectroscopic evidence, while electronic circular dichroism (ECD) calculations were used to determine their absolute configurations. In addition, gauge-including atomic orbitals (GIAO) NMR chemical shift calculation, supported by the advanced statistical method DP4 plus, was used to confirm the relative configuration of siamfuranone B (2). All the isolated compounds were evaluated against two cancer cell lines (A549 and Hela), and screened for antibacterial activities. Furthermore, they were assessed for cytotoxicity against a normal cell line (Vero cell).

Modes of Interactions with DNA/HSA Biomolecules and Comparative Cytotoxic Studies of Newly Synthesized Mononuclear Zinc(II) and Heteronuclear Platinum(II)/Zinc(II) Complexes toward Colorectal Cancer Cells.

A series of mono- and heteronuclear platinum(II) and zinc(II) complexes with 4,4',4″-tri-tert-butyl-2,2':6',2″-terpyridine ligand were synthesized and characterized. The DNA and protein binding properties of [ZnCl2(terpytBu)] (C1), [{cis-PtCl(NH3)2(µ-pyrazine)ZnCl(terpytBu)}](ClO4)2 (C2), [{trans-PtCl(NH3)2(µ-pyrazine)ZnCl(terpytBu)}](ClO4)2 (C3), [{cis-PtCl(NH3)2(µ-4,4'-bipyridyl)ZnCl(terpytBu)}](CIO4)2 (C4) and [{trans-PtCl(NH3)2(µ-4,4'-bipyridyl)ZnCl(terpytBu)}](CIO4)2 (C5) (where terpytBu = 4,4',4″-tri-tert-butyl-2,2':6',2″-terpyridine), were investigated by electronic absorption, fluorescence spectroscopic, and molecular docking methods. Complexes featuring transplatin exhibited lower Kb and Ksv constant values compared to cisplatin analogs. The lowest Ksv value belonged to complex C1, while C4 exhibited the highest. Molecular docking studies reveal that the binding of complex C1 to DNA is due to van der Waals forces, while that of C2-C5 is due to conventional hydrogen bonds and van der Waals forces. The tested complexes exhibited variable cytotoxicity toward mouse colorectal carcinoma (CT26), human colorectal carcinoma (HCT116 and SW480), and non-cancerous mouse mesenchymal stem cells (mMSC). Particularly, the mononuclear C1 complex showed pronounced selectivity toward cancer cells over non-cancerous mMSC. The C1 complex notably induced apoptosis in CT26 cells, effectively arrested the cell cycle in the G0/G1 phase, and selectively down-regulated Cyclin D.

Biosynthesis, Characterization, and Biomedical Applications of Gold Nanoparticles with Cucurbita moschata Duchesne Ex Poiret Peel Aqueous Extracts.

In this study, AuNPs were biosynthesized from Cucurbita moschata fruit peel extracts. Biosynthesized AuNPs exhibited maximum absorbance at a 555 nm wavelength, and XRD analysis indicated that the CM-AuNPs had a particle size of less than 100 nm and a cubic crystal structure. TEM scans revealed that the gold particles exhibited a spherical morphology, with an average size of 18.10 nm. FTIR analysis revealed strong peaks indicating the presence of functional groups involved in the reduction reactions. The surface charge of the biosynthesized AuNPs was determined to be -19.7 mV. The antibacterial and antifungal activities of AuNPs against pathogen strains were assessed by the minimum inhibitory concentration (MIC) method. The cytotoxic effects of CM-AuNPs on cancer cell lines (Sk-Ov-3, CaCo2, and A549) and healthy cell lines (HUVEC) were investigated using the MTT method. The findings indicated that AuNPs biosynthesized by the green synthesis method using C. moschata peel aqueous extract had high inhibition on the growth of pathogenic microorganisms and effective cytotoxic activity against cancerous cell lines at low doses. As a result, it can be concluded that CM-AuNPs will be eminently effective in the production of antibacterial and/or anticancer drugs in the pharmaceutical, food, and cosmetic industries.