Abstract:
:A series of new 2,4,6-trisubstituted pyrimidines and their N-alkyl bromide derivatives were prepared based upon methoxy substituted azachalcones as the starting materials. All newly synthesized compounds were screened for their anti-proliferative, cytotoxic, antibacterial activities and DNA/protein binding affinity. In vitro cell proliferation inhibitory and cell cytotoxic effects of 2,4,6-trisubstituted pyrimidines (1-9) and their N-alkyl bromide derivatives (2a-c, 3a-c,5a-c,6a-c, 8a-c, 9a-c) were obtained with the help of the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) cell proliferation, LDH cytotoxicity detection, and microdilution assays. The antimicrobial activity for these compounds was also evaluated following the European Pharmacopoeia 8.0 protocol. The interactions of these compounds with DNA or bovine serum albumin were investigated by the spectrophotometric titration method. When the cytotoxic analysis and anticancer properties of the compounds were examined, most of the compounds significantly exhibited an anti-proliferative potency on cancer cells (IC50 ∼ 2-10 µg/mL) and caused a cytotoxic effect as low as control drugs, 5-fluorouracil, and cisplatin (∼7-15%). Because the compound-DNA adducts are hyperchromic or hypochromic, they caused variations in their spectra. This situation shows they can be linked to DNA by the groove binding mode at a binding constant range of 2.0 × 104 and 2.4 × 105 M-1. The antimicrobial screening results revealed that our new compounds for some human Gram(+) and Gram(-) pathogen bacteria showed remarkable activity with MIC values between <7.81 and 125 µg/mL. Overall, incorporation of alkyl chain to pyrimidines in the generation of N-alkyl bromides has resulted in showing differences in DNA/protein binding affinity, along with anti-proliferative and cytotoxic activity in favor of new compounds.
journal_name
Bioorg Chemjournal_title
Bioorganic chemistryauthors
Kahriman N,Serdaroğlu V,Peker K,Aydın A,Usta A,Fandaklı S,Yaylı Ndoi
10.1016/j.bioorg.2018.10.068subject
Has Abstractpub_date
2019-03-01 00:00:00pages
580-594eissn
0045-2068issn
1090-2120pii
S0045-2068(18)30743-0journal_volume
83pub_type
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