Synthesis of Some Novel Substituted Purine Derivatives As Potential Anticancer, Anti‐HIV‐1 and Antimicrobial Agents

Abstract

In search of novel purine antimetabolites, a series of 8-substituted methylxanthine derivatives was prepared in order to explore their in vitro anticancer, anti-HIV-1 and antimicrobial activities. The target compounds include: 8-[(3-substituted-4-oxo-thiazolidin-2-ylidene)hydrazino]-1,3-dimethyl (or 1,3,7-trimethyl)-3,7-dihydropurine-2,6-diones 5a-e, 8-[(3,4-disubstituted 2,3-dihydrothiazol-2-ylidene)hydrazino]-1,3,7-trimethyl-3,7-dihydropurine-2,6-diones 6a-d and 8-(5-amino-3-arylpyrazol-1-yl)-1,3-dimethyl- (or 1,3,7-trimethyl)-3,7-dihydropurine-2,6-diones 7a-g. The in vitro anticancer results revealed that compound 5d exhibited a super sensitivity profile towards leukemia K-562 with a GI(50) value of <0.01 microM. Compound 7c showed significant activity against colon cancer HCT-15 and renal cancer CAKI-1 (GI(50) values of 0.47 and 0.78 microM, respectively). Compound 7a displayed high activity against colon cancer HCT-15 (GI(50 )= 0.8 microM). The anti-HIV-1 results indicated that compound 6b displayed a good reduction of viral cytopathic effect (56.69%). The antimicrobial results showed that compound 5a was four times more active than ampicillin against P. aerugenosa (MIC =or< 25 microg/mL), compound 5b had twice the activity of ampicillin, while compounds 5d, 7c and 7f were equipotent to ampicillin. On the other hand, compound 7a was equipotent to ampicillin against P. vulgaris (MIC = 50 microg/mL).

Lipidomic Analysis of the Outer Membrane Vesicles from Paired Polymyxin-Susceptible and -Resistant Klebsiella pneumoniae Clinical Isolates

“…The cationic l- α,γ-diaminobutyric acid residues of the polymyxin molecule produce an electrostatic attraction to the negatively charged lipid A phosphate groups, displacing the divalent cations (Mg 2+ and Ca 2+ ) [8]. The displacement leads to the disorganization of the LPS leaflet, enabling the insertion of the hydrophobic tail and the hydrophobic side chains of amino acids 6 and 7 of the polymyxin molecule into the OM [24]. Polymyxin resistance in K. pneumoniae primarily involves the multi-tier upregulation of capsular polysaccharide expression, and the systems required for the modification of lipid A with 4-amino-4-deoxy- l- arabinose and palmitoyl addition [20,23,25,26,27,28,29,30,31,32].…”

A convenient synthesis and molecular modeling study of novel purine and pyrimidine derivatives as CDK2/cyclin A3 inhibitors

“…However, some have been reported only during the last few years. In brief, the biological activities of most of the purine derivatives are briefly described 9 as potential anticancer, anti-HIV-1, antimicrobial agents and in some cases, syntheses are formulated.…”

A Base-Catalyzed Cascade Route to Phenolic 6-Cyanopurines via O-Alkylformamidoximes

“…Purines are valuable compounds with special impact in the area of medicinal chemistry, with a number of derivatives presenting antifungal, 1,2 antibacterial, 1,2 antimycobacterial, 2 anticancer, 3 and antiviral 4 activity. The synthesis of substituted purines has been addressed in several review articles, but only a few 8-aryl-6-cyanopurines have been reported from 8-bromo, 5 8-methyl 6 or 8-carbonyl 7 substitution on the purine scaffold.…”