Cytotoxicity Of New Compounds Research Articles

Tetramethylalloxazines as efficient singlet oxygen photosensitizers and potential redox-sensitive agents

Tetramethylalloxazines (TMeAll) have been found to have a high quantum yield of singlet oxygen generation when used as photosensitizers. Their electronic structure and transition energies (S0 → Si, S0 → Ti, T1 → Ti) were calculated using DFT and TD-DFT methods and compared to experimental absorption spectra. Generally, TMeAll display an energy diagram similar to other derivatives belonging to the alloxazine class of compounds, namely π,π* transitions are accompanied by closely located n,π* transitions. Photophysical data such as quantum yields of fluorescence, fluorescence lifetimes, and nonradiative rate constants were also studied in methanol (MeOH), acetonitrile (ACN), and 1,2-dichloroethane (DCE). The transient absorption spectra were also analyzed. To assess cytotoxicity of new compounds, a hemolytic assay was performed using human red blood cells (RBC) in vitro. Subsequently, fluorescence lifetime imaging experiments (FLIM) were performed on RBC under physiological and oxidative stress conditions alone or in the presence of TMeAll allowing for pinpointing changes caused by those compounds on the intracellular environment of these cells.

Ursane-Type Triterpenes with a Phenylpropanoid Unit from Camellia ptilosperma and Evaluation of Their Cytotoxic Activities.

Six new ursane-type triterpenes with a phenylpropanoid unit and five known oleanane-type triterpenes were isolated from the leaves of Camellia ptilosperma. The undescribed compounds were identified by analysis of 1D and 2D NMR and HRESIMS spectroscopic data as ptilospermanols A-F. The cytotoxicity of new compounds against six human cancer cell lines and three mouse tumor cell lines was evaluated by MTT assay.

Tetrahydroxanthone–chromanone heterodimers from lichen Usnea aciculifera and their cytotoxic activity against human cancer cell lines

Four new tetrahydroxanthone–chromanone heterodimers, usneaxanthones E–H (1–4) together with eleven known compounds (5–15) were isolated from lichen Usnea aciculifera Vain (Parmeliaceae). Their structures and absolute configurations, particularly the central and axial chiralities, were unambiguously demonstrated by a combination of spectroscopic data (1D, 2D NMR, HRESIMS), electronic circular dichroism (ECD) experiments, and single-crystal X-ray crystallographic analyses. The cytotoxicity of new compounds was evaluated on four human cancer cell lines including HCT116 colorectal cancer, MCF-7 breast cancer, A549 lung cancer, and OVCAR-3 ovarian cancer. Compounds 1–4 exhibited good cytotoxicity against all tested cancer cell lines, except ovarian cancer, with the best IC50 value of 3.37 μM. All compounds showed potent cytotoxicity against HCT116 colon cancer with IC50 value from 3.37 to 4.53 μM.

The effect of quercetin and exercise in rat metabolic syndrome model

Two series of sulfonylpiperazines linked [1,3]dioxolo[4,5-g]chromenones were synthesized featuring phenyl (7a-k) and chalcone (12a-k) bridge representing flavones or homoisoflavonoids core. New molecules are synthesized utilizing aldol condensation to inspect as antioxidants against DPPH and ABTS+ and antiproliferative agents toward selected human cancer cell lines. Cytotoxicity of new compounds was confirmed using SRB assay against non-cancer MDCK cell line. The results concluded that both individual structures of 7 and 12 were vital for modulating pharmacological potencies and presence of different electron withdrawing and electron donating functional group(s) on the phenylsulfonyl entity yielded varied biological effects. Substituent h (OCF3) and j, k (OCH3) were found to play a crucial role scavenging DPPH and ABTS+ as well as inhibiting cancer cell lines SK-OV-3 and HT-29. Moreover, molecules bearing halogen atom(s) such as substituent b-g expressed excellent inhibitory potential against HeLa and A-549 cancerous cell lines. Bioassay data displayed some interesting structure-activity relationships which are discussed in this paper. The results justified that tested derivatives are promising antioxidants and cytotoxic agents and warrant further structural optimization and bioassay studies. Spectroscopic techniques such as FT-IR, 1H NMR, 13C NMR and elemental analysis (CHN) were carried out to confirm the final structures.

Phenylsulfonyl piperazine bridged [1,3]dioxolo[4,5-g]chromenones as promising antiproliferative and antioxidant agents

Two series of sulfonylpiperazines linked [1,3]dioxolo[4,5-g]chromenones were synthesized featuring phenyl (7a-k) and chalcone (12a-k) bridge representing flavones or homoisoflavonoids core. New molecules are synthesized utilizing aldol condensation to inspect as antioxidants against DPPH and ABTS+ and antiproliferative agents toward selected human cancer cell lines. Cytotoxicity of new compounds was confirmed using SRB assay against non-cancer MDCK cell line. The results concluded that both individual structures of 7 and 12 were vital for modulating pharmacological potencies and presence of different electron withdrawing and electron donating functional group(s) on the phenylsulfonyl entity yielded varied biological effects. Substituent h (OCF3) and j, k (OCH3) were found to play a crucial role scavenging DPPH and ABTS+ as well as inhibiting cancer cell lines SK-OV-3 and HT-29. Moreover, molecules bearing halogen atom(s) such as substituent b-g expressed excellent inhibitory potential against HeLa and A-549 cancerous cell lines. Bioassay data displayed some interesting structure-activity relationships which are discussed in this paper. The results justified that tested derivatives are promising antioxidants and cytotoxic agents and warrant further structural optimization and bioassay studies. Spectroscopic techniques such as FT-IR, 1H NMR, 13C NMR and elemental analysis (CHN) were carried out to confirm the final structures.

Pyrrolo[1,2-a]azepines Coupled with Benzothiazole and Fluorinated Aryl Thiourea Scaffolds as Promising Antioxidant and Anticancer Agents.

Cancer remains a major health concern throughout history and is responsible for huge numbers of deaths globally. The sensitivity of cancer cells to anticancer drugs is a crucial factor for developing effective treatments. Pyrrolo[1,2-a]azepines coupled with benzothiazole and fluorinated aryl thiourea scaffolds have been synthesized, and their potential as cytotoxic agents was investigated against different cancer cell lines such as human ovarian cancer (SK-OV-3), cervical cancer (HeLa), colon adenocarcinoma (HT-29) and non-small-cell lung carcinoma (A549). Cytotoxicity of new compounds was confirmed using SRB assay against non-cancer MDCK cell line. In addition, free radical scavenging activity of new pyrrolo[1,2-a]azepines was examined by adopting DPPH and ABTS assays. The results concluded that the presence and position of fluorine atom(s) on the thiourea unit played a significant role in order to gain anticipated efficacies. Results of the cytotoxic assay against non-cancer MDCK cells showed that these new derivatives are safe to study further. New structures were confirmed using spectral and elemental analyses. Pyrrolo[1,2-a]azepines endowed with a benzothiazole entity and fluorinated aryl thiourea substituents were derived aiming to furnish remarkable antioxidant and anticancer activities. New molecules generated showed interesting biological result correlated with the structure and substituent of the final derivatives. Specifically, numbers and position of fluorine atoms on the thiourea unit influenced the biological profile of the mentioned compounds.

Involvement of α-methylene-γ- and δ-lactones in the suppression of multidrug resistance in MCF-7 cells.

The development of multidrug resistance to chemotherapy remains a challenge in the treatment of cancer and is a major factor causing failure of many forms of chemotherapy. The ATP binding cassette (ABC) family of proteins are efflux pumps that transport various potentially dangerous substances out of the cells. Several of the ABC transporters are related to chemoresistance, as the rapidly dividing malignant cells use them to protect themselves from medical interventions. Inhibitors of ABC transporters have the potential to enhance the efficacy of anticancer drugs. Two new synthetic compounds, AD-06 and AD-013, were tested as possible multidrug resistance inhibitors in MCF-7 cells. The cytotoxicity of new compounds was tested in MCF-7 and MCF-10A cell lines using the MTT method. Gene expression was measured by real-time PCR and changes in the protein levels were evaluated by flow cytometry and ELISA. A method based on the use of a fluorescent dye, being a marker of the ABC transporter activity, was used for screening the tested compounds as potential multidrug resistance inhibitors. AD-06 and AD-013 down-regulated NF-κB mRNA levels and decreased the population of cells with activated NF-κB. Both compounds were found to be strong ABCB1 and ABCG2 transporter inhibitors. They showed synergistic effects when incubated with taxol or oxaliplatin. α-Methylene-γ- and -δ-lactones AD-06 and AD-013 are promising lead structures for further development as multidrug resistance inhibitors.

Bioactive new withanolides from the cultured soft coral Sinularia brassica

Continuing study of the ethyl acetate (EtOAc) extract of the cultured soft coral Sinularia brassica afforded five new withanolides, sinubrasolides H–L (1–5). The structures of the new compounds were elucidated on the basis of spectroscopic analysis. The cytotoxicities of new compounds 1–5 and a known compound sinubrasolide A (6) against the proliferation of a limited panel of cancer cell lines were assayed. The anti-inflammatory activities of compounds 1–6 were evaluated by measuring their ability to suppress N-formyl-methionyl-leucyl-phenyl-alanine/cytochalasin B (fMLP/CB)-induced superoxide anion generation and elastase release in human neutrophils.

Synthesis, anti-oxidant activity, and cytotoxicity of salicyloyl derivatives of estra-1,3,5(10)-triene and androst-5-ene

AbstractSince many estrane and androstane derivatives exhibit cytotoxic, anti-oxidant, or anti-hormone activity, new steroidal derivatives were synthesised from appropriate estrogen or androgen precursors in order to obtain potential therapeutics for the treatment of steroid-dependent diseases. Starting from estradiol (I), 6-oxo derivatives V and VII were prepared. 17β-Salicyloyl-6-oxo derivatives VI and VIII were synthesised by the reaction of compounds V or VII with methyl salicylate in the presence of sodium. 17β-Salicyloyloxy estradiol IX was prepared from estradiol. Beckmann fragmentation of 16-oxyimino alcohols XII and XIII with methyl salicylate yielded corresponding D-seco derivatives XIV and XV. Simultaneous fragmentation and acylation of compound XII resulted in 3β-salicyloyl-D-seco derivative XVI which was also obtained from compound XIV. Anti-oxidant assays of the newly synthesised compounds V-IX, XIV, and XVI indicated a stronger capacity for hydroxyl radical scavenging, and a weaker capacity for DPPH radical scavenging, compared with the standard anti-oxidants BHA and BHT. Compounds V, XIV, and XVI showed higher or the same activity as BHT. The cytotoxicity of new compounds was evaluated against human breast and prostate carcinoma cells. Compound VI exhibited strong cytotoxicity against MDA-MB-231 cells; compound XIV exhibited strong cytotoxicity against PC-3 cell line, while compound VII moderately inhibited the growth of PC-3 cells.

Synthesis of 4-substituted 3-[3-(dialkylaminomethyl)indol-1-yl]maleimides and study of their ability to inhibit protein kinase C-α, prevent development of multiple drug resistance of tumor cells and cytotoxicity

A series of 3-[3-(dialkylaminomethyl)indol-1-yl]maleimides containing the indole, dihydroindole, mercaptophenol, or tetrahydroquinoline residues at position 4 of the maleimide ring, as well as 3-(dialkylaminomethyl)indole derivatives have been synthesized. Their ability to inhibit in vitro protein kinase C-α (PKC-α) has been studied. Cytotoxicity of new compounds and their ability to constrain activation of multiple drug resistance (MDR) have been studied in the human tumor cell line. Both the toxic and the low-toxic PKC-α inhibitors prevent the activation of MDR in the tumor cells. Among compounds under study, a number of substances have been found that prevent the activation of MDR but do not inhibit PKC-α.

Development of potential anti‐cancer agents: Diazenes and derivatives

AbstractThe call for the discovery of more effective agents to treat cancer has become urgent. Recently, we have synthesized new compounds: diazenes. So far, we have demonstrated that several of them inhibited the growth of tumor cells, but their solubility and biological activity were relatively low. Therefore, new compounds have been synthesized to improve their solubility and biological efficacy. In the present study, we screened cytotoxicity of 26 new diazenes and their derivatives on human cervical carcinoma HeLa cells. The most active compound was tested also on human laryngeal carcinoma, breast adenocarcinoma, and glioblastoma cells, as well as on two drug‐resistant sublines derived from cervical and laryngeal carcinoma cells. Cytotoxicity of new compounds was determined using a colorimetric MTT assay. Results show that diazene SB‐681 was the most efficient one, reducing significantly survival of HeLa cells, with IC50 value of 16.3 μM. This compound applied in low doses inhibited also the growth of other cell lines tested, among which were two drug‐resistant cell lines. The observed activity could be explained by the influence of groups attached to the diazene functionality, namely 2‐chloroethylaminocarbonyl moiety and pentafluorophenyl moiety attached to the diazene nitrogen‐nitrogen double bond. Our data indicate that SB‐681 is a promising leading compound in the development of a novel class of antineoplastic agents. Drug Dev. Res. 61:95–100, 2004. © 2004 Wiley‐Liss, Inc.