4 research outputs found
Screening of natural products for therapeutic activity against solid tumors
258-264Most of the
currently used cancer therapeutics are natural products. These agents were
generally discovered based on their toxicity to tumour cells using various
bioassays. Although the exact mechanisms of action of the most commonly used
cancer therapeutics such as anthracyclins, podophyllotoxins and camptothecin
are incompletely understood, it is becoming increasingly clear that these
agents often show complex modes of action at the cellular level, interacting
with numerous targets. Such complex modes of action may be the very reason for
clinical efficacy. For discovering new cytotoxic anticancer drugs sophisticated
screening methods were used. The principles of such screening projects
conducted, using collections of purified natural products or extracts from
plants have been described. By performing simple but robust pre-screening tests
such as the brine shrimp assay, bioactive extracts can be identified. Extracts
(65) prepared from a collection of Egyptian plants were identified that showed
cytotoxity on HepG2 cells. Interestingly, 22 (33%) of these raw extracts,
induced > 2-fold induction of caspase-cleavage activity in a colon carcinoma
cell line, consistent with induction of apoptosis. Only a fraction of the diversity of the
biosphere has been tested for biological activity and novel cancer therapeutics
remains to be discovered
Nonclassical antifolates, part 4. 5-(2-Aminothiazol-4-yl)-4-phenyl-4H1,2,4-triazole-3-thiols as a new class of DHFR inhibitors: Synthesis, biological evaluation and molecular modeling study
A new series of compounds possessing 5-(2-aminothiazol-4-yl)-4-phenyl-4H-1,2,4-triazole-3-thiol skeleton was designed, synthesized, and evaluated for their in vitro DHFR inhibition, antimicrobial, antitumor and schistosomicidal activities. Four active compounds were allocated, the antibacterial 22 (comparable to gentamicin and ciprofloxacin), the schistosomicidal 29 (comparable to praziquantel), the DHFR inhibitor 34 (IC 0.03 mM, 2.7 fold more active than MTX), and the antitumor 36 (comparable to doxorubicin). Molecular modeling studies concluded that recognition with key amino acid Leu4 and Val1
is essential for DHFR binding. Flexible alignment and surface mapping revealed that the obtained model could be useful for the development of new class of DHFR inhibitors