Synthesis of Peptide Nucleic Acids Containing Pyridazine Derivatives As Cytosine and Thymine Analogs, and Their Duplexes with Complementary Oligodeoxynucleotides

Abstract

Synthesis of peptide nucleic acids (PNAs) is reported with new pyridazine-type nucleobases: 3-aminopyridazine (aPz) and 1-aminophthalazine (aPh) as cytosine analogs, and pyridazin-3-one (Pz(O)) and phthalazin-1-one (Ph(O)) as thymine analogs. The PNAs having an aPz or a Pz(O) formed duplexes with each complementary oligodeoxynucleotide forming a base pair with G or A, respectively, as evaluated by using UV melting analyses and circular dichroism (CD) spectra.

Synthesis of Some New Pyridazine Derivatives for Anti-HAV Evaluation

“…Pyridazine-based frameworks are widely distributed in biologically active products with anti-viral [ 15 , 16 , 17 , 18 , 19 , 20 ], anti-inflammatory [ 21 , 22 , 23 , 24 , 25 ], anti-microbial [ 26 , 27 , 28 ], anti-cancer [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ], anti-convulsant [ 37 , 38 , 39 , 40 ], anti-analgesic [ 41 , 42 ], anti-tubercular [ 43 , 44 , 45 ], anti-hypertensive [ 3 , 46 ], anti-diabetic [ 47 ], anti-depressant [ 48 , 49 ], anti-Alzheimer’s [ 50 , 51 ], phosphodiesterase [ 52 , 53 ], platelet aggregation [ 54 , 55 , 56 , 57 ], and cholesterol acyl transferase inhibitor properties [ 58 ]. Peptide nucleic acids (PNAs) with new pyridazine-type nucleobases were reported as replacements for the DNA duplex bases instead of thymine, adenine, guanine and cytosine to form novel DNA or RNA duplexes [ 59 ]. Hepatitis A is a highly contagious liver infection caused by the hepatitis A virus (HAV); it is usually transmitted by the fecal-oral route, either through person-to-person contact...…”