The rapid growth of drug-resistant bacteria all over the world has given rise to a major research challenge, namely a search for alternative treatments to which bacteria will be unable to develop resistance. Photodynamic therapy is an approach of this kind. It involves the use of photosensitizers in combination with visible light at a certain wavelength to excite the former and generate reactive oxygen species. Various synthetic heterocyclic compounds are used as photosensitizers. Of these, derivatives of natural chlorophylls have a special place due to their properties. This review deals with the use of such compounds in antimicrobial PDT.

Objectives. This study aims to obtain the amino acid derivatives of chlorophyll a and bacteriochlorophyll a for the targeted delivery of pigments to tumor foci. This will increase biocompatibility and, as a result, reduce toxic side effects. In addition to photodynamic efficiency, an additional cytotoxic effect is expected for the obtained conjugates of photosensitizers (PSs) with amino acids. This is owing to the participation of the latter in intracellular biochemical processes, including interaction with the components of the glutathione antioxidant system, leading to the vulnerability of tumor cells to oxidative stress.Methods. In this work, we have implemented the optimization of the structure of a highly efficient infrared PS based on O-propyloxim-N-propoxybacteriopurpurinimide (DPBP), absorbing at 800 nm and showing photodynamic efficacy for the treatment of deep-seated and pigmented tumors, by introducing L-lysine, L-arginine, methionine sulfoximine (MSO), and buthionine sulfoximine (BSO) methyl esters. The structure of the obtained compounds was proved by mass spectrometry and nuclear magnetic resonance spectroscopy, and the photoinduced cytotoxicity was studied in vitro on the HeLa cell line.Results. Conjugates of DPBP with amino acids and their derivatives, such as lysine, arginine, MSO, and BSO have been prepared. The chelating ability of DPBP conjugate with lysine was shown, and its Sn(IV) complex was obtained.Conclusions. Biological testing of DPBP with MSO and BSO showed a 5–6-fold increase in photoinduced cytotoxicity compared to the parent DPBP PS. Additionally, a high internalization of pigments by tumor cells was found, and the dark cytotoxicity (in the absence of irradiation) of DPBP-MSO and DPBP-BSO increased fourfold compared to the initial DPBP compound. This can be explained by the participation of methionine derivatives in the biochemical processes of the tumor cell.

Background:: Conventional antitumor Photosensitizers (PS) are normally low toxic in the dark whereas light activation triggers massive cell death (photodynamic therapy, PDT).Objective:: To expand the therapeutic potential of PS to dual potency cytocidal agents, taking advantage of the use of bacteriopurpurin for a deeper tissue penetration of light, and suitability of the tetrapyrrolic macrocycle for chemical modifications at its periphery.Methods:: Conjugation of a pro-oxidant thiolate Au (I) moiety to the bacteriopurpurin core and evaluation of cytotoxicity in cell culture and in vivo.Results:: New water-soluble derivatives showed micromolar cytotoxicity for cultured human tumor cell lines in the dark, including the subline with an altered drug response due to p53 inactivation. Cellular PDT with the selected conjugate, thiolate Au (I)-dipropoxybacteriopurpurinimide (compound 6) with two triphenylphosphine Au fragments, triggered rapid (within minutes) cell death. Damage to the plasma membrane (necrosis) was a hallmark of cell death by compound 6 both in the dark and upon light activation. Furthermore, one single i.v. injection of compound 6 caused retardation of transplanted syngeneic tumors at the tolerable dose. Illumination of tumors that accumulated compound 6 significantly synergized with the effect of 6 in the dark.Conclusion:: Complexes of virtually non-toxic, photoactivatable bacteriopurpurin with the gold-containing organic moiety are considered the dual potency antitumor agents, tentatively applicable for intractable tumors.

The development of sulfur-containing pharmaceutical compounds is important in the advancement of medicinal chemistry. Photosensitizers (PS) that acquire new properties upon incorporation of sulfur-containing groups or individual sulfur atoms into their structure are not neglected, either. In this work, a synthesis of sulfur-containing derivatives of natural chlorophyll a using Lawesson’s reagent was optimized. Thiocarbonyl chlorins were shown to have a significant bathochromic shift in the absorption and fluorescence bands. The feasibility of functionalizing the thiocarbonyl group at the macrocycle periphery by formation of a Pt(II) metal complex in the chemotherapeutic agent cisplatin was shown. The chemical stability of the resulting conjugate in aqueous solution was studied, and it was found to possess a high cytotoxic activity against sarcoma S37 tumor cells that results from the combined photodynamic and chemotherapeutic effect on these cells.