Synthesis, DNA binding and in-vitro cytotoxicity studies of novel bis-pyrazoles

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1. Introduction
The Pyrazoles were an important class of compounds, since they have been proven as, extremely useful intermediates in the synthesis of new biological targets. The pyrazole ring system was found to be a versatile component in numerous pharmacological and agro chemically important compounds, heterocycles with fused pyrazoles were known to contribute to various chemotherapeutic activities like, antimicrobial [1-9], free radical scavenging [10], anti-inflammatory [11-13], analgesic, antipyretic and antiviral [14-15]. The pyrazole derivatives were also reported as inhibitors of HIV-1 reverse transcriptase [16], sodium-hydrogen ion exchanger NHE-1[17], and dipeptidase IV (DPP-IV) inhibitors [18]. Several compounds of this type were found to function as antagonists of the αvβ3 receptors, which are present on the surface of many tumor cells [19], and insecticides in agro chemistry [20]. Several lines of evidence support the view that, chemotherapy has become one of the most significant treatment modalities in cancer management. Consequently, the principal obstacle to the clinical effectiveness of chemotherapy was based on its possible toxicity to normal tissues of the body, beside the development of cellular drug resistance especially to conventional anticancer agents [21, 22]. Over the past two decades, pyrazole-containing compounds have received considerable attention owing to their different chemotherapeutic potential including versatile anti-neoplastic activities. The literature survey revealed that some pyrazole was implemented as antileukemic [23-25], antitumor [26-29], and anti-proliferative agents [30, 31], besides their capability to exert remarkable anticancer effects through inhibiting different types of enzymes...

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3. Conclusion
In summary, a series of novel bis-pyrazoles with amides, sulfonamides (6a-o) and ureas (6p-t) were synthesized and subjected to DNA binding studies. The binding pattern was analyzed through an AUTODOCK server in that 6h showed lowest conformational energy than other compounds. Then all the above compounds were evaluated for their in vitro cytotoxicity against Panc-1 (human pancreatic adenocarcinoma), H460 (human non small cell lung carcinoma) cell lines by a WST-1 cytotoxicity assay. Among them, 6a and 6b were identified as lead molecules since both were exhibited promising activity towards both the cancer cell lines. The compounds 6k and 6l were found to exhibit the activity particularly towards the pancreatic cell line and hence continuing studies to substantiate and improve activity profiles are underway in our laboratory.

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