In Vitro Anticancer Properties of Novel Bis-Triazoles.

Here, we describe the anticancer activity of our novel bis-triazoles MS47 and MS49, developed previously as G-quadruplex stabilizers, focusing specifically upon the human melanoma MDA-MB-435 cell line. At the National Cancer Institute (NCI), USA, bis-triazole MS47 (NCS 778438) was evaluated against a panel of sixty human cancer cell lines, and showed selective, distinct multi-log differential patterns of activity, with GI50 and LC50 values in the sub-micromolar range against human cancer cells. MS47 showed highly selective cytotoxicity towards human melanoma, ovarian, CNS and colon cancer cell lines; in contrast, the leukemia cell lines interestingly showed resistance to MS47 cytotoxic activity. Further studies revealed the potent cell growth inhibiting properties of MS47 and MS49 against the human melanoma MDA-MB-435 cell line, as verified by MTT assays; both ligands were more potent against cancer cells than MRC-5 fetal lung fibroblasts (SI > 9). Melanoma colony formation was significantly suppressed by MS47 and MS49, and time- and dose-dependent apoptosis induction was also observed. Furthermore, MS47 significantly arrested melanoma cells at the G0/G1 cell cycle phase. While the expression levels of Hsp90 protein in melanoma cells were significantly decreased by MS49, corroborating its binding to the G4-DNA promoter of the Hsp90 gene. Both ligands failed to induce senescence in the human melanoma cells after 72 h of treatment, corroborating their weak stabilization of the telomeric G4-DNA.

Challenges for microcirculation research in developing countries.

BACKGROUND: Microvascular dysfunction is a main contributor to morbidity and mortality worldwide. Sophisticated technical tools (e.g. miniaturized hardware, automated software), along with skilled personnel are the prerequisite for quantitative observations of the microvasculature. OBJECTIVE: This review aimed to get an overview about on-going microcirculatory research in developing countries, particularly of the South-East Asia region for the last five years and to project the challenges faced in microcirculation research in developing countries. METHODS: Original research articles originating from 194 countries were searched in PubMed database on the field of microcirculation research for the last five years. RESULTS: Our findings showed that around 1800 articles have been published from developing countries compared to more than 5000 from developed countries on different aspects of microcirculation. The overall publication per million populations for developing countries was found to be 0.37 where for developed countries it was 3.62. CONCLUSIONS: Initiation and execution of sophisticated research in microcirculation is a demand of the time. Such research, initially, may seem unmanageable in developing countries with limited resources and infrastructure settings. Collaborative scientific projects may aid in establishing networks for microvascular research in developing countries.