From food to fertilizer, algal derived products are largely employed in assorted industries, including agricultural, biomedical, food, and pharmaceutical industries. Among different chemical compositions isolated from algae, polysaccharides are the most well-established compounds, which were subjected to a variety of studies due to extensive bioactivities. Over the past few decades, the promising results for antiviral potential of algae-derived polysaccharides have advocated them as inordinate candidates for pharmaceutical research. Numerous studies have isolated various algal polysaccharides possessing antiviral activities, including carrageenan, alginate, fucan, laminaran, and naviculan. In addition, different mechanisms of action have been reported for these polysaccharides, such as inhibiting the binding or internalization of virus into the host cells or suppressing DNA replication and protein synthesis. This review strives for compiling previous antiviral studies of algae-derived polysaccharides and their mechanism of action towards their development as natural antiviral agents for future investigations.
Tribenzyltin carboxylates complexes, namely tri(4-fluorobenzyl)tin[(N,N-diisopropylcarbamothioyl)sulfanyl]acetate (C1) and tribenzyltin isonicotinate (C9), have been reported to exhibit significant anticancer activity via the death receptor and mitochondrial apoptotic pathway. However, understanding their upstream mechanism remains crucial. This study utilized both in silico and in vitro approaches to elucidate their mechanism of action. Molecular docking analysis indicated that C1 and C9 interacted with the minor groove of DNA. Fluorescence displacement assays confirmed their interaction with DNA through the minor groove. In enzyme inhibition assays, C1 showed significant inhibition of thioredoxin reductase (TrxR) activity, while C9 exhibited a dose-dependent effect, consistent with their docking affinities (- 4.1 and - 4.3 kcal/mol, respectively). Both compounds strongly inhibited human DNA topoisomerase I (TopI), supported by docking energies of - 7.0 and - 6.6 kcal/mol, respectively. The nearly complete inhibition of TopI across all treatment groups highlights it as a key molecular target. Additionally, C1 and C9 bound to thymidylate synthase (TS) with docking energies of - 7.2 and - 7.7 kcal/mol, respectively, leading to a marked reduction in TS levels. Molecular dynamics simulations of the TopI, TS, and TrxR complexes revealed that both C1 and C9 maintained stable binding within their respective active sites throughout the 100 ns trajectories. In summary, C1 and C9 primarily target the DNA minor groove and inhibit key enzymes such as TopI, TrxR, and TS, shedding light on their intricate mechanisms of action. These findings underscore the potential of C1 and C9 as promising multitarget metal-based anticancer agents.
Ruthenium(II) polypyridyl complexes can intercalate DNA with high affinity and prevent cell proliferation; however, the direct impact of ruthenium-based intercalation on cellular DNA replication remains unknown. Here we show the multi-intercalator [Ru(dppz)2(PIP)](2+) (dppz = dipyridophenazine, PIP = 2-(phenyl)imidazo[4,5-f][1,10]phenanthroline) immediately stalls replication fork progression in HeLa human cervical cancer cells. In response to this replication blockade, the DNA damage response (DDR) cell signalling network is activated, with checkpoint kinase 1 (Chk1) activation indicating prolonged replication-associated DNA damage, and cell proliferation is inhibited by G1-S cell-cycle arrest. Co-incubation with a Chk1 inhibitor achieves synergistic apoptosis in cancer cells, with a significant increase in phospho(Ser139) histone H2AX (γ-H2AX) levels and foci indicating increased conversion of stalled replication forks to double-strand breaks (DSBs). Normal human epithelial cells remain unaffected by this concurrent treatment. Furthermore, pre-treatment of HeLa cells with [Ru(dppz)2(PIP)](2+) before external beam ionising radiation results in a supra-additive decrease in cell survival accompanied by increased γ-H2AX expression, indicating the compound functions as a radiosensitizer. Together, these results indicate ruthenium-based intercalation can block replication fork progression and demonstrate how these DNA-binding agents may be combined with DDR inhibitors or ionising radiation to achieve more efficient cancer cell killing.