Chlorquinaldol targets the ß-catenin and T-cell factor 4 complex and exerts anti-colorectal cancer activity.

Aberrant activation of Wnt signaling plays a critical role in the initiation and progression of colorectal cancer (CRC). Chlorquinaldol (CQD) is a topical antimicrobial agent used to treat skin infections. Little is known about the anticancer activity of CQD and its underlying mechanisms. In this study, CQD was demonstrated to inhibit Wnt/ß-catenin signaling through targeting the downstream part of this pathway. The results showed that CQD could inhibit the acetylation of ß-catenin and disrupt the interaction of ß-catenin with T-cell factor 4 (TCF4), leading to reduced binding of ß-catenin to the promoters of Wnt target genes and downregulation of the expression of these target genes. Moreover, treatment with CQD suppressed the proliferation, migration, invasion and stemness of CRC cells. In APCmin/+ mice and CRC cell xenografts, administration of CQD suppressed tumor growth and the expression of Wnt target genes c-Myc and Leucine-rich G protein-coupled receptor-5 (LGR5). These results strongly suggest that CQD may be a promising therapeutic agent in the treatment of CRC.

High in vitro and in vivo antitumor activities of Ln(III) complexes with mixed 5,7-dichloro-2-methyl-8-quinolinol and 4,4'-dimethyl-2,2'-bipyridyl chelating ligands.

Three novel Ln(III) complexes, namely, [Pm(dmbpy)(ClQ)2NO3] (1), [Yb(dmbpy)(ClQ)2NO3] (2), and [Lu(dmbpy)(ClQ)2NO3] (3), with mixed 5,7-dichloro-2-methyl-8-quinolinol (H-ClQ) and 4,4'-dimethyl-2,2'-bipyridyl (dmbpy) chelating ligands were first synthesized. The cytotoxic activity of Ln(III) complexes 1-3, H-ClQ, and dmbpy against a panel of human normal and cancer cell lines, namely, human non-small cell lung cancer cells (NCI-H460), human cervical adenocarcinoma cancer cells, human ovarian cancer cells, and human normal hepatocyte cells, were evaluated by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The three novel Ln(III) complexes showed a high in vitro antitumor activity toward the NCI-H460 with IC50 of 1.00 ±â€¯0.25 nM for 1, 5.13 ±â€¯0.44 µM for 2, and 11.87 ±â€¯0.79 µM for 3, respectively. In addition, Ln(III) complexes 1 and 2 exerted their in vitro antitumor activity/mechanism mainly via the mitochondrial death pathway and caused a G2/M phase arrest in the following order: 1 > 2. An NCI-H460 tumor xenograft mouse model was used to evaluate the Pm(III) complex 1in vivo antitumor activity. Pm(III) complex 1 showed a high in vivo antitumor activity, and the tumor growth inhibition rate (IR) was 56.0% (p < 0.05). In summary, our study on Pm(III) complex 1 revealed promising results in in vitro and in vivo antitumor activity assays.

[Microbiological evaluation of the effectiveness of gynalgin in the treatment of vaginitis]. / Ocena mikrobiologiczna skutecznosci Gynalginu w zapaleniach pochwy u kobiet.

The microbiological effectiveness of the preparation Gynalgin produced by POLFA Pharmaceutical Works in Rzeszów was assessed in cases of vulvovaginitis in 55 patients with clinically diagnosed inflammatory conditions of the lower genital tract, who were given Gynalgin tablets in 10-day courses. Vaginal smears were examined three times for the presence of bacteria, fungi and trichomonas vaginalis (before and immediately after the treatment, and two weeks later). In the initial examination in five vaginal smears mixed bacterial flora was found, in 6 smears trichomonas was present, in 4--bacteria and fungi, and in one--trichomonas and fungi. After the treatment in control examinations I and II the number of the isolated bacterial strains was lower, trichomonas was no longer present, and the number of fungi was reduced evidently. In the light of these microbiological examinations Gynalgin was found to exert a strong fungicidal, bactericidal and antitrichomonal activity, and the results of laboratory investigations agreed with those of clinical trials of Gynalgin effectiveness.

Effects of highly active novel artemisinin-chloroquinoline hybrid compounds on ß-hematin formation, parasite morphology and endocytosis in Plasmodium falciparum.

4-Aminoquinolines were hybridized with artemisinin and 1,4-naphthoquinone derivatives via the Ugi-four-component condensation reaction, and their biological activities investigated. The artemisinin-containing compounds 6a-c and its salt 6c-citrate were the most active target compounds in the antiplasmodial assays. However, despite the potent in vitro activities, they also displayed cytotoxicity against a mammalian cell-line, and had lower therapeutic indices than chloroquine. Morphological changes in parasites treated with these artemisinin-containing hybrid compounds were similar to those observed after addition of artemisinin. These hybrid compounds appeared to share mechanism(s) of action with both chloroquine and artemisinin: they exhibited potent ß-hematin inhibitory activities; they caused an increase in accumulation of hemoglobin within the parasites that was intermediate between the increase observed with artesunate and chloroquine; and they also appeared to inhibit endocytosis as suggested by the decrease in the number of transport vesicles in the parasites. No cross-resistance with chloroquine was observed for these hybrid compounds, despite the fact that they contained the chloroquinoline moiety. The hybridization strategy therefore appeared to be borrowing the best from both classes of antimalarials.

[Antibacterial activity of chlorquinaldol esters and 2-styryl-substituted derivatives]. / Izsledvane na antibakteriinata aktivnost na niakoi esteri i zamesteni 2-stirilni proizvodni na khlorkhinaldola.

Studied was the bacteriostatic activity of a total of 17 new esters and replaced 2-styryl derivatives of chlorquinaldol. Determined were also the lowest concentrations that suppressed the growth of organisms. Some of the compounds showed higher activity and broader spectrum of antibacterial qualities, mainly against Escherichia coli, Salmonella gallinarum, and Salmonella cholerae suis as compared to the initial therapeutic preparation chlorquinaldol. It was found that the presence of chlorine atoms either in the second or in the second and fourth place in the benzene nucleus of the esters studied, the presence of a NO2-group in the third place of the same nucleus, and the presence of an extranuclear hydroxyacetyl remainder in the ester grouping could lead to a rise of the antibacterial activity. The presence of an F atom in the second and third place of the benzene nucleus of the sterile grouping also raised the activity of these compounds.

[In vitro activity of an antiseptic, chlorquinaldol, against Neisseria gonorrhoeae and Chlamydia trachomatis]. / Activité in vitro d'un antiseptique, le chlorquinaldol, sur Neisseria gonorrhoeae et Chlamydia trachomatis.

The activity of chlorquinaldol, a derivative of hydroxy-8-quinolein used for local antisepsy, was studied against Neisseria gonorrhoeae and Chlamydia trachomatis. The weak solubility of the product and the special growth conditions of the organisms made an adaptation of the AFNOR norm necessary. For 0.1 to 0.2% (W/V) chlorquinaldol concentrations, a reduction of about 10(4) organisms was obtained after 60 minutes for N. gonorrhoeae and C. trachomatis. However, for technical problems, the concentrations tested were 10 to 100 times lower than the doses usually recommended for this antiseptic.

In vitro sensitivity of Trichomonas vaginalis and Candida albicans to chemotherapeutic agents.

Strains of fresh clinical isolates of Trichomonas vaginalis and Candida albicans have been tested in vitro for their sensitivity to eight drugs used in the therapy of monilial and trichomonal vaginitis. Three of the chemotherapeutic agents, chlorchinaldol, clotrimazole and broxyquinoline were effective against both organisms. Tinidazole and metronidazole were active against T. vaginalis. The strains of C. albicans were also sensitive to trichomycin, natamycin and nystatin. Tinidazole was the most effective trichomonacide, clotrimazole and chlorchinaldol were most effective against C. albicans, while chlorchinaldol had the best in vitro effect against both organisms. The ranges of the MICs are compared to values previously reported.