Purine-benzimidazole hybrids: synthesis, single crystal determination and in vitro evaluation of antitumor activities.
In an effort to identify novel compounds for the treatment of cancer, a diverse array of potential bioactive hybrid, purine-benzimidazole was synthesized in good yields through nucleophilic substitution at C6 position of purine ring with versatile cyclic amines at C2 position. The structures of newly prepared compounds were confirmed by IR, (1)H, (13)C NMR, mass spectroscopy and, in case of 19, by single crystal X-ray diffraction analysis. The newly synthesized compounds were evaluated against 60 human tumour cell lines at one dose concentration level. Compound 6 exhibited significant growth inhibition and was evaluated as 60 cell panel at five dose concentration levels. Compound 6 proved to be 1.25 fold more active than the positive control 5-FU, with GI50 value of 18.12 μM (MG-MID). Interaction of the compounds with Aurora-A enzyme involved in the process of propagation of cancer, has also been investigated. Compound 6 showed selectivity towards Aurora-A kinase inhibition with IC50 value of 0.0l μM. Molecular docking studies in the active binding site provided theoretical support for the experimental biological data acquired.
School of Chemistry and Biochemistry, Thapar University, Patiala 147004, India.
Alka
A
Sharma
School of Chemistry and Biochemistry, Thapar University, Patiala 147004, India.
Vijay
V
Luxami
School of Chemistry and Biochemistry, Thapar University, Patiala 147004, India. Electronic address: kpaul@thapar.edu.
Kamaldeep
K
Paul
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D064096:Aurora Kinase A / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D062105:Molecular Docking Simulation; D011687:Purines / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship
D000970:Antineoplastic Agents; D001562:Benzimidazoles; D011687:Purines; C031000:benzimidazole; D064096:Aurora Kinase A; C030985:purine
Antitumor activity; Aurora kinase inhibitor; Benzimidazole; Molecular modeling; Purine; X-ray structure