Cytotoxic evaluation of volatile oil from Descurainia sophia seeds on MCF-7 and HeLa cell lines.

Descurainia sophia is a plant widely distributed and used as folk medicine throughout the world. Different extracts of aerial parts and seeds of this plant have been shown to inhibit the growth of different cancer cell lines in vitro. In this study, cytotoxic activity of D. sophia seed volatile oil was evaluated. D. sophia seed powder was mixed with distilled water and left at 25 °C for 17 h (E1), 23 h (E2) and 28 h (E3) to autolyse. Then, the volatile fractions of E1, E2, and E3 were collected after steam distillation for 3 h. Cytotoxic effects of the volatile oils alone or in combination with doxorubicin (mixture of E1 or E2 at 50 µg/ml or E1 at 100 µg/ml with doxorubicin at 0.1, 1, 10 µM) against MCF-7 cell line were determined using MTT assay. Cytotoxic effect of E1 volatile oil was also determined on HeLa cell line. The results indicated that 1-buten-4-isothiocyanate was the major isothiocyanate found in the volatile oils. The results of cytotoxic evaluations showed that volatile constituents were more toxic on MCF-7 cells with IC50< 100 µg/ml than HeLa cells with IC50> 100 µg/ml. No significant differences were observed between cytotoxic activities of E1, E2 and E3 on MCF-7 cell line. Concomitant use of E1 and E2 (50 µg/ml) with doxurubicin (1 µM) significantly reduced the viability of MCF-7 cells compared to the negative control, doxorubicin alone, or each volatile fraction. The same result was obtained on HeLa cells, when E1 (100 µg/ml) was concurrently used with doxorubicin (1 µM).

Synthesis and characterization of folate-targeted dextran/retinoic acid micelles for doxorubicin delivery in acute leukemia.

Folate and retinoic acid grafted/dextran (FA-RA/DEX) copolymers with different molecular weight of DEX were synthesized using carbonyldiimidazole and dimethylaminopyridine for targeted delivery of doxorubicin (DOX) in acute myelogenous leukemia (AML). The copolymers structure was confirmed by (1)H NMR and FTIR. Critical micelle concentration (CMC) of each copolymer was determined using pyrene as a fluorescent probe. DOX was loaded in micelles by the direct dissolution method. Physical properties of micelles, including particle size, zeta potential, drug loading efficiency, and drug release profiles, were examined. The orientation of the folate ligand on the surface of the micelles was studied by X-ray photoelectron spectroscopy (XPS) technique. The cytotoxicity of micelles loaded with DOX at different concentrations was studied in KG1 cells using MTT assay and their cellular uptake by flow cytometry technique. FTIR and (1)H NMR spectra confirmed successful production of the targeted micelles and XPS spectra showed the surface orientation of folate. R15D10F7 copolymer produced micelles with particle size of 82.86 nm, polydispersity index of 0.3, zeta potential of -4.68 mV, drug loading efficiency of 96%, and release efficiency of 63%. DOX loaded in folate-targeted micelles of RA/DEX was more toxic than that in nontargeted micelles and free drug and seems promising in reducing drug resistance in AML.

Synthesis of some new 2,3-disubstituted-4(3H)quinazolinone derivatives.

Quinazolinones are interesting materials because of their valuable biological effects. In this study some new 2,3-disubstituted-4(3H)quinqzolinone derivatives were synthesized from anthranilic acid in six steps by introducing a new chiral center to the aliphatic side chain of the quinazolinone. In the last step, a single acylation on the hydrazine moiety afforded final compounds. The structures of compounds were confirmed by IR, (1)HNMR and Mass spectra.

Antibacterial, antifungal and cytotoxic evaluation of some new quinazolinone derivatives.

Quinazolinone ring system is renown because of its wide spectrum of pharmacological activities due to various substitutions on this ring system. In this study, the minimum inhibitory concentration of the synthesized compounds in our laboratory was determined by micro dilution Alamar Blue(®) Assay against six strains of bacteria (three Gram-positive and three Gram-negative) and three strains of fungi. Following a broth micro dilution minimum inhibitory concentration (MIC) test, Minimum Bactericidal Concentration (MBC) and Minimum Fungicidal Concentration (MFC) tests were performed. Cytotoxic effects of the compounds were measured using the MTT colorimetric assay on HeLa cell line. Results of antimicrobial screening showed that compounds had better bacteriostatic activity against Gram-negative bacteria. Results from MBC revealed that these compounds had more significant bacteriostatic than bactericidal activities. Nearly all screened compounds showed good activity against C. albicans and A. niger. Results from MFC indicated that these compounds had better fungistatic rather than fungicidal activities. The synthesized target molecules were found to exhibit different cytotoxicity in the range of 10 to 100 µM on HeLa cell line. Compounds 6 and 7 exhibited acceptable cytotoxicity approximately 50% at 10 µM concentration.

Synthesis and cytotoxic evaluation of some new 4(3H)-quinazolinones on HeLa cell line.

Quinazolinone backbone is present in a large number of bioactive substances. Since remarkable cytotoxic activity is associated with some 4(3H)-quinazolinones, in this study some 4(3H)-quinazolinone were synthesized and screened against HeLa cells. The synthesis was performed via reaction of anthranilic acid with dicarboxylic anhydrides to produce carboxylic acids derivatives. The products were heated in acetic anhydride to produce benzoxazinones. Finally, 4(3H)-quinazolinones were synthesized by reaction between benzoxazinones and primary amines. The assessment of the structure of the synthesized compounds was based on spectral data (FT-IR, Mass and (1)HNMR). Subsequently, cytotoxic activity of compounds 3, 6, 9 and 13 (individually and in combination with doxorubicin) was evaluated on HeLa cell line using MTT assay. The results indicated that the tested compounds did not show significant cytotoxicity alone and in combination with doxorubicin (1 and 20 µM).

Antibacterial, antifungal and cytotoxic evaluation of some new 2,3-disubstituted 4(3H)-quinazolinone derivatives.

In this study antibacterial, antifungal and cytotoxic effects of some new 2,3-disubstituted 4(3H)-quinazolinone derivatives have been evaluated. The in vitro antibacterial and antifungal tests of new synthesized compounds were performed using MABA method against six strains of bacteria (three Grampositive and three Gram-negative) and three strains of fungi. Also Minimum Bactericidal Concentration (MBC) and Minimum Fungicidal Concentration (MFC) tests were performed. All synthesized compounds indicated mild antibacterial effects especially against Gram-negative bacteria. The most sensitive bacteriumwas E. coli. All strains of tested fungi were sensitive to the synthesized compounds mostly at 32 µg/ml and there was no significant differences in the sensitivity of the tested compounds. MBC and MFC data indicated that tested compounds act as bactriostatic and fungistatic agents. Cytotoxic activity of the compounds was screened at 1, 10 and 100 µM concentrations against HeLa cells using the MTT colorimetric assay. While the synthesized compounds did not show significant cytotoxic activities, compounds 7a(3) and 7a(4) reduced cell viability to about 50% at 100 µM concentration. The present study revealed that most of the new synthesized compounds possess good antifungal effects and they could be considered as valuable candidates for further structural modification to design more potent antifungal agents.

Synthesis of some new tricyclic 4(3H)-quinazolinone derivatives.

Quinazolinones are interesting molecules with a wide range of biological activities. We prepared a number of quinazolinone derivatives by the condensation of 5-bromo- or 5-nitro-substituted anthranilic acids with chloro-acyl chlorides. Anthranilic acid derivatives were treated with either 3-chloro-propionyl chloride or 4-chloro-butyryl chloride to yield the corresponding N-acyl-anthranilic acids. The resultants were reacted with acetic anhydride to afford the benzoxazinone intermediates, which upon condensation with elected amines in either DMF or ethanol gave the corresponding tricyclic 4(3H)-quinazolinone derivatives. It was found that reactions in DMF produced higher yields.

Synthesis and anti-inflammatory activity of new 1-methyl-4-(4-X-benzenesulfonyl)pyrrolo[2,3-d] imidazole-5-carboxylates.

A series of 1-methyl-4-(4-X-arylsulfonyl)pyrrolo[2,3-d]imidazo-le-5-carboxylates were synthesized and tested as anti-inflammatory agents. Indomethacin was used as reference drug. Two of the synthesized compounds 7a and 7b had an effect equal to 0.1 of indomethacin. Our result showed that the electron-withdrawing substituents in the para position of the benzensulfonyl moiety increase activity.