The DIA-DB is a web
server for the prediction of diabetes drugs
that uses two different and complementary approaches: (a) comparison
by shape similarity against a curated database of approved antidiabetic
drugs and experimental small molecules and (b) inverse virtual screening
of the input molecules chosen by the users against a set of therapeutic
protein targets identified as key elements in diabetes. As a proof
of concept DIA-DB was successfully applied in an integral workflow
for the identification of the antidiabetic chemical profile in a complex
crude plant extract. To this end, we conducted the extraction and
LC-MS based chemical profile analysis of Sclerocarya
birrea and subsequently utilized this data as input
for our server. The server is open to all users, registration is not
necessary, and a detailed report with the results of the prediction
is sent to the user by email once calculations are completed. This
is a novel public domain database and web server specific for diabetes
drugs and can be accessed online through .
Quercetin is a flavonoid presenting cytotoxicity against different cancer cell lines. We hypothesized that its core could serve as a scaffold for generating more potent compounds. A quercetin-alanine bioconjugate was synthesized, its cellular internalization was monitored through confocal microscopy and its cytotoxic activity was explored against ten different cell lines. The bioconjugate consistently illustrated enhanced cytotoxic activity with respect to the parent compound. A threefold enhancement in its cytotoxicity was revealed for HeLa, A549, MCF-7 and LNCaP cells. In silico studies suggested that quercetin-alanine possesses enhanced binding affinity to human estrogen receptor alpha corroborating to its activity to MCF-7, overexpressing this receptor. Spectrofluorimetric, calorimetric and in silico studies revealed that quercetin-alanine binds primarily to Sudlow site I of serum albumin mainly through hydrogen bonding. Through this array of experiments we discovered that the specific compound bears a more refined pharmaceutical profile in contrast to quercetin in terms of cytotoxicity, while at the same time preserves its affinity to serum albumin. Natural products could thus offer a potent scaffold to develop bioconjugates with amplified therapeutic window.
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