Furan-Conjugated Tripeptides as Potent Antitumor Drugs.

Cervical cancer is among the leading causes of death in women. Chemotherapy options available for cervical cancer include highly cytotoxic drugs such as taxol, cisplatin, 5-florouracil, and doxorubicin, which are not specific. In the current study, we have identified a new peptide conjugate (Fur4-2-Nal3-Ala2-Phe1-CONH2) (conjugate 4), from screening of a small library of tripeptide-conjugates of furan, as highly potent anticancer compound against human cervical cancer cells (HeLa cells) (IC50 = 0.15 ± 0.05 µg/mL or 0.28 +/- 0.09 µM). Peptides were constructed on Rink amide resin from C- to N-terminus followed by capping by α-furoic acid moiety. The synthesized peptides were purified by recycling RP-HPLC, and structures of all the peptides were confirmed by using FABMS/ESIMS, 1H- NMR, 13C-NMR, and HR-FABMS. Conjugate 4 was furthermore found to be specifically active against human cervical cancer cells since it did not inhibit the proliferation of other human normal cells (HUVEC (human umbilical vein endothelial cells) and IMR-90 (normal human fibroblasts)), and cancer cells tested (HUVEC, MCF-7, and MDA-MB-231 cells), as well as in mice 3T3 cells (normal fibroblasts). This study revealed a good structure activity relationship of various peptide conjugates. Conjugate 4 in branched forms (4a and 4b) were also synthesized and evaluated against HeLa cells, and results revealed that both were inactive. Atomic force microscopy (AFM) studies and staining with rhodamine 123 and propidium iodide (PI) revealed that conjugate 4 possesses a membranolytic effect and causes the loss of mitochondrial membrane potential.

Potent leishmanicidal and antibacterial metabolites from Olea ferruginea.

Inspired from the leishmanicidal and antibacterial potential of the fractions obtained from the crude extract of Olea ferruginea stem, the anti-leishmanial ethyl acetate fraction was subjected to chromatographic separation, leading to the isolation of a new compound ferruginan (1) and a known compound (+)- cycloolivil (2). The structures of 1 and 2 were determined by various spectroscopic techniques and were assayed for their in vitro antibacterial and leishmanicidal potential. Compound 1 showed 75% inhibition after 24 h of incubation and 98% inhibition after 48 h of incubation against Leishmania tropica KWH23 promastigotes at 100 µg/mL concentration, while compound 2 exhibited 73% and 96% inhibition at the same concentration and incubation time. Compound 1 also showed good activity against various bacterial pathogens.