KB Cancer Cell Lines Research Articles

Development of technetium-99m labeled ultrafine gold nanobioconjugates for targeted imaging of folate receptor positive cancers

IntroductionStrategic design and synthesis of nanoparticle based preparations could improve diagnostic screening of several cancer types, thereby facilitating better clinical management of the disease. Towards this, the present work aims to develop and evaluate a radioactive technetium-99m (99mTc) labeled gold nanoparticle (NP) preparation modified with folic acid, so as to diagnose folate receptor positive cancers viz. ovarian, breast, etc. Methods11-Bromoundecanoic acid (UA) was synthetically modified both with folic acid and Hydrazinonicotinic acid (HYNIC) chelate at the carboxylic acid end and subsequently converted to thiol functionality at the bromo terminal to yield folic acid-UA-SH and HYNIC-UA-SH ligands respectively. Gold NPs modified with folic acid and HYNIC chelator were obtained on direct addition of folic acid-UA-SH and HYNIC-UA-SH to chloroauric acid in polysorbate 80 solution under reducing conditions. These NPs were then radiolabeled with 99mTc following HYNIC labeling approach. Both the inactive and 99mTc-labeled gold NPs were then tested for their biological efficacy in folate receptor (FR) positive KB cancer cell lines. Also, biodistribution studies of 99mTc-labeled gold NPs were carried in KB tumor xenografts to ascertain the efficacy towards FR in in vivo system. ResultsPolysorbate 80 could stabilize the gold NP preparation with average size <10 nm as determined by TEM. Inhibition of [3H]folic acid with functionalized gold nanoparticle revealed affinity towards FR positive KB cell lines with an IC50 ~ 9 μM. Biodistribution studies of 99mTc-labeled gold NP preparation in SCID mice bearing KB tumor showed an uptake of 1.39 ± 0.18%ID/g in tumor and 5.48 ± 0.72%ID/g in kidneys at 3 h post-injection. In vivo distribution in folic acid pre-treated animals could not establish the specificity towards folate receptors. ConclusionsBiological evaluation of functionalized gold NP showed affinity towards FR positive cancer cell lines. 99mTc-labeled NP exhibited target uptake in both in vitro and in vivo models, but folic acid inhibition could not establish the target specificity. Nevertheless, in vivo pharmacokinetics envisaged in the present design was achieved using the present gold functionalized NP preparation.

Synthesis, structure and in vitro cytotoxicity testing of some 2-aroylbenzofuran-3-ols.

Five 2-aroyl-5-bromobenzo[b]furan-3-ol compounds (two of which are new) and four new 2-aroyl-5-iodobenzo[b]furan-3-ol compounds were synthesized starting from salicylic acid. The compounds were characterized by mass spectrometry and 1H NMR and 13C NMR spectroscopy. Single-crystal X-ray diffraction studies of four compounds, namely, (5-bromo-3-hydroxybenzofuran-2-yl)(4-fluorophenyl)methanone, C15H8BrFO3, (5-bromo-3-hydroxybenzofuran-2-yl)(4-chlorophenyl)methanone, C15H8BrClO3, (5-bromo-3-hydroxybenzofuran-2-yl)(4-bromophenyl)methanone, C15H8Br2O3, and (4-bromophenyl)(3-hydroxy-5-iodobenzofuran-2-yl)methanone, C15H8BrIO3, were also carried out. The compounds were tested for their in vitro cytotoxicity on the four human cancer cell lines KB, Hep-G2, Lu-1 and MCF7. Six compounds show good inhibiting abilities on Hep-G2 cells, with IC50 values of 1.39-8.03 µM.

Design and Synthesis of Novel Coumarin Conjugated Acetamides as Promising Anticancer Agents: An In Silico and In Vitro Approach.

Coumarin and benzophenone possess a vast sphere of biological activities, whereas thiazoles display various pharmacological properties. Hence, present study focused on the incorporation of coumarin and thiazole core to the benzophenone skeleton to enhance the bioactivity, anticipating their interesting biological properties. The objective of the current work is the synthesis and biological evaluation of a novel series of coumarin fused thiazole derivatives. A novel series of coumarin conjugated thiazolyl acetamide hybrid derivatives were synthesized by a multistep reaction sequence and were characterized by the FT-IR, LCMS, and NMR spectral techniques. The newly synthesized compounds were screened for anti-cancer activity by in silico and in vitro methods. The cytotoxicity of the synthesized unique compounds was executed for two different cancer cell lines, MCF-7 (Breast cancer) and KB (Oral cancer), in comparison with standard paclitaxel by MTT assay. The compound 7f is a potent motif with an acceptable range of IC50 values, for anti-cancer activity, i.e., 63.54μg/ml and 55.67μg/ml, against the MCF-7 and KB cell lines, respectively. Molecule docking model revealed that this compound formed three conventional hydrogen bonds with the active sites of the amino acids, MET 769, ARG 817, and LYS 721. Compound 7f with two methyl groups on the phenoxy ring and one 4-position methoxy group on the benzoyl ring, showed a significant cytotoxic effect. An advantageous level of low toxicity against normal cell line (L292) by MTT assay was determined.

Synthesis, Characterization, and In Vitro Cytotoxicity of Platinum(II) Complexes Bearing Chiral Tetradentate Salicylaldimine Ligands

A series of platinum(II) complexes with chiral Schiff base ligands derived from various salicylaldehydes with (R,R′)- and (S,S′)-cyclohexanediamine were synthesized and characterized by ESI-MS, IR, and NMR. Obtained spectra with typical signals were in agreement with suggested molecular formulae of the complexes. Their photophysical properties were studied by UV-visible and emission spectroscopies. The UV-Vis showed the typical band with low energy at visible range 400–500 nm for MLCT, and this band can emit the luminescent band with emission maximum wavelengths at 529–595 nm. The in vitro cytotoxicity of obtained platinum(II) complexes was screened for KB and MCF-7 human cancer cell lines. The results showed that (S)-enantiomers were more active than (R)-enantiomers and the different positions of methoxy group in salicyl ring gave different cytotoxicities.

Design, Synthesis, and Cytotoxic Evaluation of Novel Lupane Triterpenoid Derived Hydroxamates

A series of new hydroxamate derivatives of lupane triterpenoids has been designed and successfully synthesized. The synthesized compounds were evaluated for their in vitro antitumor activity using the 3-[4,5-dimethylthiazol-2-yl]−2,5-diphenyltetrazolium bromide-based assay against the human cancer cell lines KB and HepG2. Most of these derivatives possess at least moderate cytotoxic activity and the hydroxamate derivative compounds 3c, 3e, 7a, and 15b could be lead compounds for further optimization to develop novel anticancer agents.

Stilbenes from Macaranga tanarius (Euphorbiaceae) growing in Vietnam

AbstractMacaranga tanarius is a medium‐sized tree that is widespread in the Southeast Asian and western Pacific regions. The ethyl acetate extract of this species was showed cytotoxic activity against KB cancer cell line. In this article, we report the isolation and structural elucidation of four known stilbenes from fruit glandular trichomes of M. tanarius including vedelianin (1), schweinfurthins E‐G (2‐4). The structures of the isolated compounds were elucidated from their mass and NMR spectral data. Cytotoxic activity of the isolated compounds (1‐4) against KB cell line was also discussed.

Organocatalyzed synthesis and biological activity evaluation of hybrid compounds 4H-pyrano[2,3-b]pyridine derivatives

1,4-Dihydropyridines and 4H-pyran derivatives are common and important structures in various pharmaceutical compounds. Dihydropyridines are well-known moieties in compounds that have analgesic, fungicidal, and antibacterial activities and 4H-pyran structures are populous in compounds with antibacterial and anti-cancer potential; exploiting the biological activities of both 1,4-dihydropyridines and 4H-pyran moieties through the exploration of hybrid compounds featuring combinations of these two heterocyclic functionalities is an interesting avenue of research. In this research, we developed novel 1,4-dihydropyridines and 4H-pyran hybrid compounds generated under organocatalytic conditions and evaluated their cytotoxic activity toward KB and HepG2 cancer cell lines.

Cytotoxic Heptaketides from the Endolichenic Fungus Ulospora bilgramii

Eleven new metabolites including nine heptaketides, ulosporin A-G (1a-7b), one diphenyl compound, ulophenol (8), and one spirobisnaphthalene, palmarumycin P5 (9), were isolated from the endolichenic fungus Ulospora bilgramii, which inhabits the lichen Umbilicaria sp. The structures of these compounds were elucidated based on comprehensive analysis of their spectroscopic, electronic circular dichroism (ECD), and single-crystal X-ray diffraction data. Ulosporin G (7) inhibited the growth of the human cancer cell lines A549, MCF-7, and KB with IC50 values of 1.3, 1.3, and 3.0 μM, respectively. Additionally, it induced A549 cell apoptosis through G0/G1 cell cycle arrest caused by DNA damage.

Paxiiones A–D, four new flavonoids from the stem of Mallotus paxii Pamp.

Phytochemical investigation of the stems of Mallotus paxii Pamp., which are used for traditional Chinese medicinal treatment of viral infections in China, led to the isolation of four new flavonoids, paxiiones, A–D (1-4). Their structures were elucidated by spectroscopic analyses, including MS, NMR (1D and 2D), X-ray, experimental CD, and calculated ECD spectra. Compounds 1-4 were evaluated for their cytotoxic activities in KB, MCF7, and HepG-2 human cancer cell lines, and they exhibited cytotoxic activities, with IC50 values ranging from 8.62 μM to 48.21 μM. Compound 1 in particular showed significant cytotoxic activity in the KB cell line, with an IC50 value 8.62 μM.

Anticancer and antiproliferative efficacy of a standardized extract of Vaccinium macrocarpon on the highly differentiating oral cancer KB cell line athwart the cytotoxicity evaluation of the same on the normal fibroblast L929 cell line.

Background and Objectives:The perpetual search is on to find botanical complementary adjuncts to the conventional therapies used that is not only cost-effective but also reduces side effects associated with conventional synthetic drugs that are available in the market. The aim of this study was to assess the in vitro anticancer efficacy of hydroalcoholic fruit extract of cranberry against oral cancer KB cell line by Di-Methyl Thiazoldiphenyl Tetrazolium bromide assay (MTT) assay and its cytotoxicity on normal fibroblast cells.Materials and Methods:Vaccinium macrocarpon extract was prepared using a hydroethanolic solvent (water – 30%:ethanol – 70%) using the standardized maceration protocol. Standard KB and normal fibroblast (L929) cell lines were used. The minimum lethal effect of the extract was calculated using the MTT cytotoxicity assay.Results:The extract shows a satisfactory antiproliferative effect on the KB cell line and a higher cell viability percentage of the normal fibroblast cell line.Conclusion:V. macrocarpon can prove to be an adjunct to the existing anticancer drug therapy against oral cancer KB cell line.

Gas Chromatography-High-Resolution Mass Spectrometry Elucidation and in vitro Cell Line Studies (Sulforhodamine B) on Niosomal Gel of Benincasa hispida

Background: The Cucurbitaceae family has been known for its presence of phytoconstituents, namely, lupeol, β-sitosterol, terpenoids, phenols, and proteins with therapeutic potential. Objectives: The research paper tries to focus on major therapeutic field of people demographic area of type of cancer. Soxhlet extraction of Benincasa hispida (BH) was carried out and crude extract was converted to powder. Niosomal gel was formulated after the optimization of drug concentration from the extract of Niosomal solution. Solution with maximum entrapment was selected for the preparation of gel. Gel was prepared by using different Carbopol grades and with comparison of different parameters. Gel was studied for gas chromatography-high-resolution mass spectrometry (GC-HRMS) evaluation for check toxicity. Biologic activity was analyzed by SRB (Sulforhodamine B) assay with in vitro cell lines (human oral cancer cell line KB and Mus Musculus skin melanoma B16-F10). Results: Solution which was clear and white was selected for gel development. Carbopol 934 (1') as gelling agent showed good formulation properties. It was non-gritty, easily spreadable, and washable. The gel with maximum entrapment efficiency was evaluated further. GC-HRMS revealed 1.2-ethyl 2-Hexen-1-ol; 1,8-(3-Octyl-2-oxiranyl)-1-octanol; Dodecanoic acid, 2-penten-1-yl ester; Cholestane, 4, 5-epoxy-,(4α,5α); Cyclopentaneundecanoic acid; 17-octadecynoic acid; Octadecanoic acid, methyl ester; Methyl oleate; Tridecanoic acid, methyl ester; and Silane, dimethyl (2,3,6, tricholrophenoxy) heptadicycloxy. The selected cell lines did not show satisfactory activity at different concentrations in SRB assay. Conclusion: This research paper tried to witness the probable potential of BH for cancer with analytical base. Future studies may be undertaken at various stages and levels to further explore the potential of these families of plants.

In-vitro Anti-cancer assay and apoptotic cell pathway of newly synthesized benzoxazole-N-heterocyclic hybrids as potent tyrosine kinase inhibitors.

A series of benzoxazole-N-heterocyclic hybrids have been synthesized by a one-pot strategy. Molecular docking study revealed that such compounds have the ability to inhibit enzyme protein tyrosine kinase. The findings of this work have been the successful synthesis of benzoxazole scaffolds, featuring hybrids of benzoxazole with quinoline and quinoxaline respectively. The molecular docking studies have showed these compounds to be inhibitors of tyrosine kinase enzyme which triggers growth of cancer cells. The cytotoxicity study of compounds 4a-f showed better potency against breast cancer cell lines MCF-7 and MDA-MB-231 in contrast to oral and lung cancer cell lines KB and A549. The tyrosine kinase activity was measured using Universal Tyrosine Kinase Assay kit using horseradish peroxide (HRP)-conjugated anti-phosphotyrosine kinase solution as a substrate. The compounds 4c exhibited maximum inhibition in the activity of enzyme tyrosine kinase with IC50 value 0.10 ± 0.16 µM, than other compounds which were studied and thus proved to be inhibitors of enzyme tyrosine kinase. The selective index of all four compounds was found out to be greater than two, indicating the non-toxic behaviour, i.e. good anti-cancer activity. Further, fluorescence microscopic study helped to characterize the mode of cell death, which was found to be late apoptosis as indicated by the orange fluorescence. The SAR analysis has also been carried out.

A new isoflavanone from Uraria crinita

A new isoflavanone, (3S)-5,7-dihydroxy-2′,3′,4′-trimethoxy-6,5′-diprenylisoflavanone (1) and eight known compounds including five flavones (2–6), two triterpenes (7–8) and a steroid (9) were isolated from the whole plant of Uraria crinita (Leguminosae). The structure of 1 was elucidated by detailed spectroscopic means including IR, HR-ESI-MS, 1D and 2D NMR, and CD data. Compounds 1–9 were evaluated for their cytotoxicity against four human cancer cell lines KB (mouth epidermal carcinoma), HepG2 (hepatocellular carcinoma), Lu (lung carcinoma) and MCF7 (breast carcinoma). Compound 1 showed cytotoxic activity against the tested cell lines with IC50 values of 33.2, 29.4, 59.6 and 66.8 μM, respectively.

Cytotoxic prenylated flavonoids from the leaves of Macaranga indica

Three new prenylated flavonoids, macarindicins D–F (1-3) together with eight known compounds, macadenathin B (4), glyasperin A (5), kaempferol (6), quercetin (7), quercitrin (8), (+)-isolariciresinol (9), (–)-woonenoside XI (10), and (+)-lyoniresinol 4-O-β-d-glucopyranoside (11) were isolated from the leaves of Macaranga indica Wight. Their structures were determined on the basis of extensive spectroscopic methods, including 1D-, 2D-NMR and MS data. All the isolated compounds were evaluated for their cytotoxic activities against KB, MCF-7, HepG-2, and LU human cancer cell lines. As results, compound 2 showed significant cytotoxic activity on all human cancer cell lines with IC50 values ranging from 11.0 to 17.0 μM. Compounds 3-5, exhibited moderate cytotoxic activity against all human cancer cell lines with IC50 values ranging from 15.0 to 38.2 μM.

C25 steroids from the marine mussel-derived fungus Penicillium ubiquetum MMS330

Two new unusual C25 steroid epimers, 24-O-methyl-24-epi-cyclocitrinol (1) and 24-O-methylcyclocitrinol (2), together with the known oxylipin α-dimorphecolic acid (3), were isolated from the extract of cultures of a Penicillium ubiquetum MMS330 strain sampled from the blue mussel Mytilus edulis. The structures of the new compounds were established based on 1D and 2D NMR spectral analyses and CP3 conformation analysis. LC–MS dereplication of other C25 steroids in culture extracts was also performed on the basis of their HRMS/MS fragmentation patterns, allowing to detect other analogues. Biological activities of compounds 1 and 2 were evaluated as a mixture on the two human cancer cell lines KB and MCF-7.

Chemical Constituents of Microalgae Tetraselmis convolutae

The first chemical investigation of the marine microalgae Tetraselmis convolutae is reported. Two phytyl esters, phytyl hexadeca-4,7-10,13-tetraenoate (1) and phytyl palmitate (2), and five other compounds, including phytol (3), hexadeca-4,7-10,13-tetraenoic acid (4), poriferasterol (5), palmitic acid (6), and glycerol (7), were isolated from the extracts of Tetraselmis convolutae. Compound 1 was isolated from nature for the first time, and it showed significant cytotoxic activity against KB, SK-LU-1, MCF7, and HepG2 cancer cell lines with IC50 values in the range of 65.23 ± 6.17–89.81 ± 5.83 μM/mL.

Meroditerpene pyrone, tryptoquivaline and brasiliamide derivatives from the fungus Neosartorya pseudofischeri

Two new meroditerpene pyrones, chevalone F (1) and 11-hydroxychevalone E (2), a new tryptoquivaline analog, tryptoquivaline V (3) and a new brasiliamide analog, brasiliamide G (4), together with thirteen known compounds, chevalones A-C (5–7), chevalone E (8), 11-hydroxychevalone C (9), pyripyropene A (10), isochaetominine C (11), pyrrolobenzoxazine terpenoids CJ-12662 (12) and CJ-12663 (13), fischerindoline (14), eurochevalierine (15), 1,4-diacetyl-2,5-dibenzylpiperazine-3,7′′-oxide (16) and lecanorin (17) were isolated from the fungus Neosartorya pseudofischeri. Their structures were established on the basis of spectroscopic evidence. Compound 2 showed weak antibacterial activity against Escherichia coli and Salmonella enterica serovar Typhimurium, whereas compounds 7, 12, 13 and 15 showed antibacterial activity against Bacillus cereus and Staphylococcus aureus. In addition, compounds 13 and 14 showed cytotoxicity against KB and MCF-7 cancer cell lines, as well as the Vero cell line.

Novel Pyrazolyl Benzoxazole Conjugates: Design, Synthesis, Molecular Docking Studies and in vitro Anticancer Activities

Nowadays, hybrid drugs have gained a significant role in the treatment of different health problems. Most of the hybrid molecules with different heterocyclic moieties were proved to be potent anti-tumor agents in cancer chemotherapy. Hence, the present study is aimed at the evaluation of in vitro anticancer activity of novel hybrid molecules (pyrazolyl benzoxazole conjugates) and to investigate their anticancer activity by molecular docking studies. Designed, synthesized and characterized the novel pyrazolyl benzoxazole conjugates. Anticancer activity of these compounds was determined by SRB assay. Then molecular docking studies were carried out against proto-oncogene tyrosine-protein kinase (ATP-Src, PDB: 2BDF), a putative target for cancer. All the synthesized compound derivatives were evaluated against MCF-7, KB, Hop62 and A549 cancer cell lines. Compounds 9b and 9c exhibited excellent anticancer activities with GI50 values of &lt;0.1 µM against MCF-7 and A549 cell lines. Compound 9e exhibited good antitumor activity on MCF-7 and A-549 with GI50 values of 0.12 µM and 0.19 µM respectively. Compound 9g showed better anticancer activity on A-549 cancer cell line with GI50 of 0.34 µM. The two-hybrid molecules 9b and 9c are found to be comparably potent with the standard drug doxorubicin and may act as drug lead compounds in medicinal chemistry aspect. The present docking investigation proved that having benzoxazole of compound 9c at the position of benzofuran of reference compound (N-acetyl pyrazoline derivative) might be valid for contributing to anti-cancer activity.

Physical Absorption of Folic Acid and Chitosan on Dihydroartemisinin-Loaded Poly-Lactic-Co-Glycolic Acid Nanoparticles via Electrostatic Interaction for Their Enhanced Uptake and Anticancer Effect

In this study, dihydroartemisinin (DAR), an anticancer agent with low toxicity, was loaded into poly-lactic-co-glycolic acid (PLGA) nanoparticles. The obtained PLGA cores were then coated with chitosan (CS) and/or folic acid (FA) by electrostatic interactions to enhance their anticancer and cellular uptake properties. DAR-loaded PLGA nanoparticles were prepared by the solvent evaporation method. CS and FA solutions at different ratios were dispersed concurrently into the PLGA suspension to facilitate electrostatic interactions and form nanosuspensions. The physiochemical properties of nanoparticles such as average particle size (Z), polydispersity index (PDI), zeta potential (ZP), TEM image, X-ray diffraction, and encapsulation efficiency were determined. We then determined the role of FA and CS coating on the nanoparticle surface in cytotoxicity, cellular uptake, and apoptosis. We show that the resultant nanoparticles were spherical and uniform, with a coating layer containing FA and CS covering PLGA cores with a Z of 223.5±4.28 nm, PDI of 0.209±0.03, and ZP of 15.75±1.3 mV. Both FA and CS improved the cytotoxicity of nanoparticles compared to free DAR and PLGA nanoparticles in HL-60 and KB cancer cell lines. Further, FA enhanced the cellular uptake of nanoparticles to a greater extent than CS. However, CS contributed more to apoptosis induction than FA.

Bioactive galloyl flavans from the stems of Helixanthera parasitica

Three new flavans, (2S)-7-O-galloyl-5,3′,4′-trihydroxyflavan (1), (2S)-7,3'-O-digalloyl-5,4'-dihydroxyflavan (2), and (2S)-7,4'-O-digalloyl-5,3'-dihydroxyflavan (3), together with four known compounds, (2S)-5,7,3′,4′-tetrahydroxyflavan (4), (-)-epicatechin (5), (-)-syringaresinol (6), and methyl gallate (7) have been isolated from the EtOAc extract of the stems of Helixanthera parasitica. Compounds 2 and 3 were obtained as a mixture of positional isomers. The structures of the isolated compounds were established using extensive spectroscopic data. Compound 1 and the mixture of 2 and 3 exhibited significant antimalarial activity against Plasmodium falciparum, with IC50 values of 0.59 and 1.38 μM, respectively. In addition, flavans 1–3 showed cytotoxicity against KB, MCF-7, and NCI-H187 cancer cell lines, with IC50 values in the range of 11.1–30.0 μM.