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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Research Article

Recursive Partitioning Analysis and Anti-Tubercular Screening of 3- Aminopyrazine-2-Carbohydrazide Derivatives

Author(s): Pankaj Miniyar*, Anand Mahajan, Dattatray Anuse, Ashish Kumar, Mahesh Barmade, Dhiman Sarkar, Manisha Arkile and Vijay Khedkar

Volume 16, Issue 11, 2019

Page: [1264 - 1275] Pages: 12

DOI: 10.2174/1570180816666190329222636

Price: $65

Abstract

Background: Treating tuberculosis is a challenge due to the development of drug resistance. Hence, it is imperative to develop novel leads having high potency and efficacy to curb drug resistance.

Methods: The present research work is focused on microwave-assisted synthesis of novel twenty-six 3-amino-N’-benzylidenepyrazine-2-carbohydrazide derivatives (3a-z), where, lyophilization technique was used for isolation of the major intermediate, 3-aminopyrazin-2-carbohydrazide. All synthesized compounds were subjected for anti-tubercular screening against Mycobacterium tuberculosis H37Ra by using XTT Reduction Menadione Assay (XRMA) protocol.

Results: Out of 26 synthesized compounds, four N’-substitutedbenzaldehyde-3-amino-pyrazine-2- carbohydrazide derivatives viz. 3i, 3j 3v and 3z showed significant activity against M. tuberculosis H37Ra. The compounds 3i, 3j, 3v and 3z showed 99, 98, 92 and 87 % inhibition respectively as compared to 94% inhibition shown by the standard drug rifampicin. The MIC and IC50 values were in the range of 24.3-110 and 5.9-20.8 µg/ml respectively.

Conclusion: A classification model called Recursive Partitioning (RP) based on binary Quantitative Structure-Activity Relationship (QSAR) was derived for the establishment of structure-activity relationship (SAR). The predictions derived on the basis of RP model were found to be in agreement with anti-tubercular screening data.

Keywords: 3-aminopyrazine, carbohydrazide, anti-tubercular activity, lyophilization, QSAR, recursive partitioning.

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