Alternative Tumor-Targeting Strategies
David E. Thurston, Ilona Pysz in Chemistry and Pharmacology of Anticancer Drugs, 2021
The chemical structures of porfimer sodium and temoporfin are based on the porphyrin and closely related chlorin structures (Figure 10.28), a group of naturally occurring intensely colored compounds whose name originates in the Greek word for purple (i.e., porphura). Molecules of this type perform biologically important roles in plants, animals, and bacteria, including photosynthesis. The porphyrins are tetrapyrrolic molecules, with the overall heterocyclic macrocycle known as a porphine. The basic porphine frame consists of four pyrrolic subunits linked on opposing sides through four methine (CH) bridges known as the meso-carbon atoms/positions. The resulting conjugated planar macrocycle may be substituted at the meso- or other positions. The related chlorin structure consists of three pyrroles and one pyrroline coupled through four =CH- linkages. Unlike porphin, the central aromatic ring structure of the porphyrins, a chlorin is predominantly aromatic but not through the entire circumference of the macrocyclic ring. The chlorophyll macrocycles that provide the central photosensitive pigments in the chloroplasts of plants and bacteria are magnesium-containing chlorins. For porphyrin-based PDT agents such as porfimer sodium and temoporfin, the excited state of the porphyrin molecules after illumination with light of an appropriate wavelength and energy, and the subsequent electron spin transfer to molecular oxygen, generate singlet oxygen atoms (i.e., free radicals) which exert the cytotoxic effect.
Red Cells with High Oxygen Affinity Hemoglobins
Ronald L. Nagel in Genetically Abnormal Red Cells, 2019
Heme is the combination of a porphyrin ring and an iron molecule. The porphyrin, in turn, is composed of four pyrrole rings tied together by methenyl (=CH-) bridges. In myoglobin and hemoglobin the porphyrin ring is protoporphyrin IX, defined by the type of substitutions found in the carbons not involved in the bridging. In Figure 3 it can be seen that pyrrols 1 and 4 have methyls and propionic acids as side chains while pyrrols 2 and 3 have methyls and vinyls as side chains. All of these components are arranged in a single plane resulting in a wafer-like structure. The center piece of the structure is a tetracoordinated iron atom, in which the bonds with pyrrole ring 4 and 2 are identical. The same can be said of the bonds between the iron and pyrrole 1 and 3. This structure, weighing 616 daltons, contains a large number of alternating double bonds and consequently delocalized π electrons.
Plant Source Foods
Chuong Pham-Huy, Bruno Pham Huy in Food and Lifestyle in Health and Disease, 2022
Chlorophylls are unique pigments with green color and are found in the chloroplasts of diverse plants, algae, and cyanobacteria (15). Chlorophyll is a chelate made up of carbon, nitrogen, oxygen, and hydrogen atoms along with a magnesium metal ion in the central position. The whole chemical structure of chlorophyll is a porphyrin (6, 15). The porphyrin of chlorophyll contains four pyrrole-like rings (tetrapyrrole ring) bonded to a magnesium ion via their four nitrogen atoms in a square planar arrangement. Porphyrin structures of chlorophyll molecules are similar to those of hemoglobin and myoglobin in humans and of vitamin B12. The main difference is the presence of an iron ion in the central position of hemoglobin and myoglobin structures, and of a cobalt ion in vitamin B12 (6, 15). The numbers of naturally occurring chlorophylls may not yet be fully known. However, five classes of chlorophylls are well-known, namely a, b, c, d, and f (15). Chlorophyll a and chlorophyll b are the main components of photosystems in all photosynthetic organisms (6–7, 15–16). In green plants, most chloroplasts have three times more chlorophyll a than b (7). The green chlorophyll pigments are the source of magnesium, an essential mineral of human cell activity after calcium. Indeed, the consumption of green vegetables containing chlorophylls is indispensable for our health maintenance and for the prevention of some chronic diseases such as cancer and cardiovascular diseases due to their antioxidant activity.
Heme metabolism as a therapeutic target against protozoan parasites
Published in Journal of Drug Targeting, 2019
Guilherme Curty Lechuga, Mirian C. S. Pereira, Saulo C. Bourguignon
Metalloporphyrins are formed by metal ions coordinated with macrocycles, called porphyrins that consist of four pyrrole rings linked together through methenyl bridges [41]. These porphyrins have been identified as potent targets for interfering with the malaria parasite’s metabolism by selectively blocking heme detoxification [42,43]. The effect of heme analogues against Plasmodium falciparum is controversial. It has been shown that metalloporphyrins have low activity against P. falciparum despite their capacity to inhibit β-hematin formation [44]. In contrast, a series of porphyrin analogs and precursors showed in vitro activity against these parasites at a nanomolar range [45]. Nanoencapsulation of porphyrins enhanced, 80-fold, the antimalarial activity of Zn-protoporphyrin [46] and has been proposed as a tool to enhance drug delivery, especially since porphyrin cannot easily pass through cell membranes [33].
Porphyromonas gingivalis diffusible signaling molecules enhance Fusobacterium nucleatum biofilm formation via gene expression modulation
Published in Journal of Oral Microbiology, 2023
Yukiko Yamaguchi-Kuroda, Yuichiro Kikuchi, Eitoyo Kokubu, Kazuyuki Ishihara
The expression of fap2 increased significantly in cocultured F. nucleatum. Fap2 is a galactose inhibitable adherence factor involved in coaggregation between F. nucleatum and P. gingivalis, hemagglutination by F. nucleatum [17], and localization of F. nucleatum to colon tumors [36]. The results indicate that the sensing of diffusible signaling molecules from P. gingivalis by F. nucleatum induces an increase in fap2. The increase in Fap 2 may contribute to binding between the species and enhance these intimate interactions, although further analysis is required to confirm the magnitude of contribution. Fap2 is also involved in hemagglutination by F. nucleatum [17]. P. gingivalis has hemagglutination activity, which is involved in heme acquisition [37]. In the cocultured F. nucleatum, cobK and cbiJ expression increased. These genes are involved in porphyrin metabolism. It is possible that hemagglutination is involved in iron acquisition in F. nucleatum. Therefore, the increase in Fap2 expression may be one of the adaptations for establishing a synergistic community of F. nucleatum and P. gingivalis.
Approaches to expand the conventional toolbox for discovery and selection of antibodies with drug-like physicochemical properties
Published in mAbs, 2023
Hristo L. Svilenov, Paolo Arosio, Tim Menzen, Peter Tessier, Pietro Sormanni
A recent study by Lecerf et al. revealed that some clinical-stage antibodies interact with heme.87 Heme is an abundant prosthetic group with a porphyrin structure and a molecular mass of 616 Da. Strikingly, the binding to heme-induced polyreactivity in some of the antibodies illustrates that non-specificity can be potentiated by small molecules that are abundant in the human body.87 In addition, the authors reported that binding to heme correlates with hydrophobicity, self-association tendency and intrinsic polyreactivity.9,87 Interestingly, several antibodies in the study by Lecerf et al. also interacted with another small molecule, folate, hinting that therapeutic mAbs might be predisposed to non-specific interactions with different heterocyclic compounds.
Related Knowledge Centers
- Chlorophyll
- Heme
- Organic Compound
- Oxygen
- Pyrrole
- Circulatory System
- Macrocycle
- Locant
- Methine Group
- Hemoprotein