Solution structures of purine base analogues 6-chloroguanine, 8-azaguanine and allopurinol

Abstract

Analogues of purine bases are highly relevant in the biological context and have been implicated as drug molecules for therapy against a number of diseases. Additionally, these molecules have been implicated to have a role in the prebiotic RNA world. However, experimental data on the structures of these molecules in aqueous solution is lacking. In this work, we report the ultraviolet resonance Raman spectra of 6-chloroguanine, 8-azaguanine and allopurinol, obtained with 260 nm excitation. The reported spectra have been assigned to normal modes computed from density functional theory (B3LYP/6-31G (d,p)) calculations. This work has been useful in identifying the solution-state structures of these molecules at neutral pH. We find that the guanine analogues 6-chloroguanine and 8-azaguanine exist as keto-N9H and keto-N7H tautomers in solution, respectively. On the other hand, the hypoxanthine analogue allopurinol exists as a mixture of keto-N9H and keto-N8H tautomers in solution. We predict that this work would be particularly useful in future vibrational studies where these molecules are present in complexes with their target proteins.

Raman spectroscopic study of 6-amino-7-deazapurine

“…Analogues of purine bases have been implicated in the prebiotic system as drug molecules for therapy [10]. A compound of deazapurines as a purine-based metabolite has diverse functions ranging from secondary metabolism to RNA modification [11].…”

Natural Products with Heteroatom-Rich Ring Systems

“…Condensation of phenylacetamide 11 with anthraniloyl-CoA would generate quinazolinone 12, which, upon hydrolysis, gives amidine 13. Methionine-derived formamide (14) would then undergo condensation with amidine 13 to forge the 1,2,4-triazole and hence penipanoid A (7). This proposed biosynthesis is likely to be relevant to chrysotriazoles 8 and 9 due to their structural similarity.…”

“…The extensive biological properties of 1 are covered in a detailed review, so only a brief discussion is included herein. 8-Azaguanine ( 1 ) displays antimicrobial and cytotoxic properties against a wide range of bacteria, viruses, fungi, and human cancer cell lines. , 8-Azaguanine ( 1 ) exerts this cytotoxic activity following conversion to a nucleotide derivative that inhibits nucleic acid and protein synthesis. ,, Not included in the aforementioned review are the early investigations into the applications of 1 to treat human malignancies; these efforts were hindered by issues with administration, dosing, and resistance, leading to further investigations being abandoned . 8-Azaguanine ( 1 ) has also recently been found to act as a substrate of hypoxanthine guanine phosphoribosyl transferase in Plasmodium falciparum , thus inhibiting [ 3 H]­hypoxanthine uptake (IC 50 6.6 μM) and therefore inhibiting parasite growth (IC 50 18 μM), making it a potential lead compound in the development of novel antimalarial agents .…”

“…20 The original isolation authors subsequently attributed the erroneous data to using a crude sample of the natural product in the antibacterial assays. 20 The 1,2,4-triazole penipanoid A (7) was isolated from Penicillium paneum SD-44, a marine-sediment-derived fungus collected from the South China Sea in 2011. 22 The structure of penipanoid A (7) was assigned using X-ray crystallography.…”

“…22 The structure of penipanoid A (7) was assigned using X-ray crystallography. 22 Penipanoid A (7) displayed cytotoxic activity against the SMMC-7721 cell line with an IC 50 value of 54.2 μM; however, no antimicrobial activity was observed against an array of fungi and bacteria. 22 In 2013, the 1,2,4-triazole alkaloids chryso-triazoles A (8) and B (9) were isolated from the marine-algaderived endophytic fungus Penicillium chrysogenum EN-118.…”