PMID: J Biomol Struct Dyn. 2021 Jan 22:1-23. Epub 2021 Jan 22. PMID: 33480316 Abstract Title: Structure-activity insights of harmine targeting DNA, ROS inducing cytotoxicity with PARP mediated apoptosis against cervical cancer, anti-biofilm formation andtherapeutic study. Abstract: Harmine exhibits pH dependent structural equilibrium and possesses numerous biological and pharmacological activities. Mode and mechanism of DNA binding and its cytotoxicity were studied by multiple spectroscopic, calorimetric, molecular docking andapoptotic as well asbiochemical and histological studies. It exists as cationic (structure I) and decationic form (structure II) in the pH range 3.0-7.8 and 8.5-12.4, respectively, with a pof 8.0. Structure I at pH 6.8 binds strongly to DNA with a cooperative mode of binding of1.03 × 10Mand stoichiometry of 5.0 nucleotide phosphates. Structure I stabilized DNA by 10 °C, showed85%quenching of fluorescence intensity, perturbation in circular dichroism, partial intercalation and enthalpy driven exothermic binding. While, structure II at pH 8.5 has very weak interaction with CT DNA. Cytotoxic potencies of structure I was tested on four different cancer cell lines along with normal embryonic cell. It showed maximum cytotoxicity with GIof 20 µM, against HeLa causing several apoptotic induction abilities. Harmine exhibited G2M arrest with ROS induced effective role in PARP mediated apoptosis as well as anti-inflammatory action on HeLa cells. Harmine further presented MIC and antibiofilm activity againstin presence of
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