EUROPEAN JOURNAL OF
PHARMACEUTICAL AND MEDICAL RESEARCH

( An ISO 9001:2015 Certified International Journal )

An International Peer Reviewed Journal for Pharmaceutical, Medical & Biological Sciences

An Official Publication of Society for Advance Healthcare Research (Reg. No. : 01/01/01/31674/16)

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 ISSN 2394-3211

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Abstract

NEW SULFONYL PYRIMIDINES INDUCE APOPTOSIS THROUGH DNA CLEAVAGE PATHWAY

Priyanka Yadav, Shafia Mir, Praveen Kumar and Ayaz Mahmood Dar*

ABSTRACT

The new sulfonyl pyrimidinones (4-6) were synthesized by the reaction of sulfonyl thiosemicarbazones (1-3) with ethyl cyanoacetate in absolute ethanol. After characterization by spectral and analytical data, the DNA interactions of the compounds were carried out by UV-vis, fluorescence spectroscopy, circular dichroism, molecular docking and gel electrophoresis. The compound binds to DNA preferentially through electrostatic interactions with Kb; 2.93 ×103 M–1, 3.03 × 103 M–1 and 3.11 × 103 M–1, respectively depicting the higher propensity of compound 6 with CT DNA. Gel electrophoresis depicted that compound 6 brought conversion of SC form (Form II) into LC form (Form III) of DNA at 4.0 μM. The docking study suggested that the intercalation of compounds in between the nucleotide base pairs is due to the pyrimidinone moiety of the sulfone derivative. The circular dichroism studies suggest that compounds (4-6) affect the helicity of B-DNA. During in vitro cytotoxicity, compound (4-6) revealed potential toxicity against the different human cancer cells. AO/EB staining analysis clearly indicates that compound 5 causes apoptosis in cancer cells. The results revealed that compound 5 has better prospectus to act as a cancer chemotherapeutic candidate, which warrants further in vivo anticancer investigations.

Keywords: Sulfonyl pyrimidinones, Thiosemicarbazones, DNA binding, MTT.


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Google Scholar Indian Science Publications InfoBase Index (In Process) SOCOLAR, China Research Bible, Fuchu, Tokyo. JAPAN International Society for Research activity (ISRA) Scientific Indexing Services (SIS) Polish Scholarly Bibliography Global Impact Factor (GIF) (Under Process) Universal Impact Factor International Scientific Indexing (ISI), UAE Index Copernicus CAS (A Division of American Chemical Society) USA (Under Process) Directory of Open Access Journal (DOAJ, Sweden, in process) UDLedge Science Citation Index CiteFactor Directory Of Research Journal Indexing (DRJI) Indian citation Index (ICI) Journal Index (JI, Under Process) Directory of abstract indexing for Journals (DAIJ) Open Access Journals (Under Process) Impact Factor Services For International Journals (IFSIJ) Cosmos Impact Factor Jour Informatics (Under Process) Eurasian Scientific Journal Index (ESJI) International Innovative Journal Impact Factor (IIJIF) Science Library Index, Dubai, United Arab Emirates Pubmed Database [NLM ID: 101669306] (Under Process) IP Indexing (IP Value 2.40) Web of Science Group (Under Process) Directory of Research Journals Indexing Scholar Article Journal Index (SAJI) International Scientific Indexing ( ISI ) Scope Database Academia