We report here on the synthesis and in vitro anti-tumor effects of a series of novel 1,2,4-triazole (compounds 3–6), 4,5-dicyanoimidazole (compound 7), and purine (compounds 8–13) coumarin derivatives and their acyclic nucleoside analogues 14–18. Structures of novel compounds 3–18 were deduced from their 1H- and 13C-NMR and corresponding mass spectra. Results of anti-proliferative assays performed on a panel of selected human tumor cell lines revealed that compound 6 had moderate cytostatic activity against the HeLa cell line (IC50 = 35 µM), whereas compound 10 showed moderate activity against the HeLa (IC50 = 33 µM), HepG2 (IC50 = 25 µM) and SW620 (IC50 = 35 µM) cell lines. These compounds showed no cytotoxic effects on normal (diploid) human fibroblasts.

4-Amino-N-adamantylphthalimide (1) is a dye with moderate absorptivity (in CH3CN ε363 = 4200 M-1 cm-1) and high quantum yield of fluorescence (ΦF = 0.15-0.80) that exhibits fluorosolvatochromic properties. The dye can be excited at 405 nm and the position of fluorescence maximum and the Stokes shift are well correlated with the ET(30) parameter. The excitation in the near-visible part of the spectrum and low cytotoxicity allow use of the dye in live cell microscopy. Due to its amphiphilic character, the dye stains artificial membranes in liposomes. Using confocal microscopy on two human cancer cell lines, we have shown that 1 binds primarily to intracellular lipid droplets. Colocalization experiments with different organelle markers indicated that 1 additionally binds to mitochondrial membranes. The fluorosolvatochromism of 1 allows the simultaneous visualization of mitochondria and intracellular lipid droplets in two separate emission channels, which has a potential use in cells and tissues exhibiting intense oxidative metabolism of lipids.

Evaluation of their affinity for herpes simplex type 1 (HSV-1) and varicella-zoster virus-encoded thymidine kinases (VZV TK) also showed that none of the compounds was able to significantly inhibit 1 µM deoxythymidine phosphorylation by HSV-1 and VZV TK at 500 µM concentrations. The in vitro cytostatic activity evaluation results indicated a weak antiproliferative activity for all tested compounds. Only 6-pyrrolylpurine derivative bearing a carboxylic group substituted cyclopropane ring produced a rather slight inhibitory effect at higher micromolar concentrations on a breast carcinoma cell line (MCF-7) and no cytotoxic effect on human normal fibroblasts (WI 38). Conclusions: The lack of antiherpetic activity may be due to poor, if any, recognition of the compounds by virus-induced nucleoside kinases as an alternative substrate to become metabolically activated.The discovery of the acyclic guanosine analogue acyclovir (ACV; Figure 1) as a selective anti-herpes simplex virus (HSV) agent [1] initiated investigation of new acyclic nucleoside analogues with better antiviral activity properties than ACV. These efforts resulted in the discovery of new broad-spectrum antiviral agents: ganciclovir (GCV; Figure 1) [2][3][4] and penciclovir (PCV; Figure 1) [5,6]. In addition, the crystal structure of HSV-1-encoded thymidine kinase (TK), a key enzyme for activation of antiherpetic nucleosides, in complex with GCV, revealed the importance of the two hydroxyl groups of GCV mimicking the 3′-and 5′-hydroxyl groups of the 2′-deoxyribose moiety in natural nucleosides for substrate recognition [7].Based on these findings, (1′S, 2′R)-9-{[1′,2′-bis(hydroxymethyl)cycloprop-1-yl]methyl}guanine (A-5021; Figure 2) was developed as a nucleoside analogue that potently inhibits the replication of several herpes viruses including HSV type-1 (HSV-1) and HSV type-2 (HSV-2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV) and human herpesvirus type 6 (HHV-6). Though the sugar moiety of A-5021 has a cyclopropane ring, its overall feature is considered to be acyclic due to the flexible methylenic spacer. The antiviral activity of A-5021 is superior over ACV against HSV-1, HSV-2, . The racemic 9-{[1′,2′-bis(hydroxymethyl)cycloprop-1-yl] methyl}guanine and especially its 1′S, 2′R enantiomer

In this study, three groups of adamantylphthalimides, bearing different substituents at the phthalimide moiety, N-(4′-R 2 )phthalimidoadamantanes (1-7), 3-[N-(4′-R 2 ) phthalimido]-1-adamantanols (8-10), and 3-[N-(4′-R 2 )phthalimido]adamantane-1carboxylic acids (11-15), were synthesized and screened against tumor cells and viruses. The most potent compounds are not substituted at the adamantane and bear an OH or NH 2 substituent at the phthalimide (compounds 3 and 5). The antiproliferative activities of compounds 3 and 5 are in the micromolar range, much higher than the one of thalidomide. A minor antiviral activity against cytomegalovirus and varicella-zoster virus was found for compounds 3 and 5, but these compounds lacked selectivity. The results presented are important for the rational design of the next-generation compounds with anticancer and antiviral activities. K E Y W O R D S adamantane, antiproliferative activity, antiviral activity, phthalimide

Adamantane α‐, β‐, and δ‐amino acids activated by phthalimide (i.e., 3–6) were synthesized, and their photochemical reactivities were investigated. Amino acid derivatives 3–6 underwent a photoinduced electron transfer (PET) and decarboxylation reaction sequence, most probably through a triplet excited state. The decarboxylations of the β‐amino acid derivatives were succeeded by cyclization reactions that afforded complex polycyclic molecules with potential biological interest. The adamantyl radical that is produced by the photoinduced decarboxylation could be trapped by alkenes or oxygen to deliver adducts or alcohols, respectively. The photodecarboxylation process was shown to be more efficient under acetone sensitization conditions (with quantum yields, Φ = 0.02–0.5) than upon direct excitation, and the reactivity was dependent on the chain length (intramolecular distance) between the electron donor (carboxylate) and acceptor (phthalimide in the triplet excited state) of the derivative. The formation of different radicals, that is, the 1‐ or 2‐adamantyl intermediate, probably does not affect the overall rate of the decarboxylation This current report provides a better understanding of photodecarboxylation and the rational design of molecular systems to undergo photoinduced decarboxylation and cyclization reactions.