Tasneem A. Khwaja

Recent studies on the anticancer activities of mistletoe (Viscum album) and its alkaloids.

Detailed methods for in vitro/in vivo evaluation of anticancer drugs, with special reference to mistletoe extracts, have been reviewed. Mistletoe extracts have been shown to possess significant antitumor activity, in vivo, against murine tumors, Lewis lung carcinoma, colon adenocarcinoma 38 and C3H mammary adenocarcinoma 16/C. Methods for the extraction of biologically active alkaloids from mistletoe and their anticancer activities are presented. The possible origin of alkaloids in mistletoe plants, and their contributions towards a mechanism of anticancer activities of mistletoe extracts, are proposed.

Isolation of biologically active alkaloids from Korean mistletoeViscum album, coloratum

Anticancer activity of certain highly cytotoxic alkaloids present in Korean mistletoe has been demonstrated in experimental animals. Unlike European mistletoe, no cytotoxic proteins were found in the Korean mistletoe.

Characterization of the high pH wobble structure of the 2-aminopurine·cytosine mismatch by N-15 NMR spectroscopy

Transition mutations induced by the base analogue 2-aminopurine arise via the formation of AP.C base pairs during DNA replication. We report here the results of N-15 NMR studies on a duplex oligonucleotide containing N-15 enriched AP and C residues. At high pH (8.6) the AP.C base pair is predominantly wobble. This is the first report on use of a site specifically N-15 enriched oligonucleotide as a probe of aberrant base pairing in DNA.

In Silico Modulation of Apoptotic Bcl-2 Proteins by Mistletoe Lectin-1: Functional Consequences of Protein Modifications

The mistletoe lectin‐1 (ML‐1) modulates tumor cell apoptosis by triggering signaling cascades through the complex interplay of phosphorylation and O‐linked N‐acetylglucosamine (O‐GlcNAc) modification in pro‐ and anti‐apoptotic proteins. In particular, ML‐1 is predicted to induce dephosphorylation of Bcl‐2‐family proteins and their alternative O‐GlcNAc modification at specific, conserved Ser/Thr residues. The sites for phosphorylation and glycosylation were predicted and analyzed using Netphos 2.0 and YinOYang 1.2. The involvement of modified Ser/Thr, and among them the potential Yin Yang sites that may undergo both types of posttranslational modification, is proposed to mediate apoptosis modulation by ML‐1. J. Cell. Biochem. 103: 479–491, 2008.

Preparation of Imino and Amino N-15 Enriched 2-Aminopurine Deoxynucleoside

Abstract We report the synthesis of N-15 enriched 2-aminopurine-2′-deoxynucleoside (APdR). Both ring and 2-amino nitrogens were labelled via a Dimroth rearrangement of the free base. The corresponding deoxynucleoside was prepared enzymatically. Results of both proton and N-15 NMR studies show that the predominant tautomeric form of APdR is amino and the N1 position is shown to be the site of protonation.

Comparison of quantitative structure-activity relationships of the inhibition of leukemia cells in culture with the inhibition of dihydrofolate reductase from leukemia cells and other cell types.

A set of 2,4-diamino-5-(3-X-phenyl)-s-triazines was used to inhibit the growth of tumor cells (L5178 leukemia) in culture. The molar concentration (C) of triazine causing 50% reduction in the rate of cell growth was used to develop a quantitative structure-activity relationship: log 1/C = 1.32 pi - 1.70 log (beta.10 pi + 1) + 0.44I + 8.10, where pi is the hydrophobic constant for X, beta is a disposable parameter, and I is an indicator variable for congeners containing a -CH2Z-C6H4-Y moiety (Z = O or NH). This equation is compared with similar equations derived for the inhibition of dihydrofolate reductase from leukemia cells and bovine liver.

8-Phosphorus substituted isosteres of purine and deazapurines.

Synthesis of 8-phosphorus substituted isosteres of purine [pyrimidino (4,5-d)-1,3,2-diazaphosphole], 1-deazapurine [pyridino (2,3-d)-1,3,2-diazaphosphole] and 3-deazapurine [pyridino (4,5-d)-1,3,2-diazaphosphole] has been achieved by the reaction of equimolar amounts of triphenylphosphite and 4,5-diaminopyrimidine, 2,3-diaminopyridine and 3,4-diaminopyridine, respectively. These compounds hydrolyzed (cleavage of the phosphorus-nitrogen bounds) in aqueous solutions to provide the corresponding diaminopyrimidine or diaminopyridines. These three new basic ring systems constitute the first reported synthesis of purines in which ring carbon atom is substituted with a phosphorus atom. 8-Phosphorus substituted purine at a concentration of 4 X 10(-4)M caused a 50% inhibition in the growth of leukemia L1210 cells in culture. The biochemical rationale for the synthesis of these compounds is discussed.

Anticancer Activities of 7-, and 9-Substituted 3-Deazaguanine Derivatives

Abstract Interesting differences in anticancer activities of 7- and 9-substituted derivatives of 3-deazaguanine are described.