A Systematic Bioinformatics Approach for Multiple Virtual Screening for Finding Novel MDR-TB Antagonists: Structure Based Screens & Toxicity Prediction Analyzing Poly Pharmacological Affects
Keywords:
Drug resistant, tumorigenic properties, pharmacological optimizationAbstract
Multidrug-resistant tuberculosis has been
resistant over more than two primary drugs (isoniazid
and rifampin) resulted due to misuse and
mismanagement which leads to administration of
improper treatment regimens and failure to ensure that
patients complete the whole course of treatment.
Screening the library of MDR-TB antagonists against
the bacterial strains can improve the pharmacological
optimization compared over the primary drugs.
In the present study, virtual screening has been
introduced using surflex dock targeting mycobacterial
metabolite (DNA Gyrase) virtually screened against
chemical library of Rifampin and Isoniazid.
Consequently, HtrA2 has been virtually screened
against chemical library of ciprofloxacin, ofloxacin and
moxifloxacin according to their bio affinity and
analysed polypharmacological affects.
Derivate of Ofloxacin (ZINCID_39383034) demonstrate
better interactions with HtrA2 (PDBID_2PZD) and so
on derivate of Rifampin (ZINC_ID85907485)
demonstrate better interactions with DNA Gyrase
(PDBID_3IFZ) following Lipinski’s rule of five and
without any mutagenic, toxic or carcinogenic effects.
Comparatively, analysing the binding patterns of
derivates contrary to their primary drugs, inferred that
docking score of the derivates have been significant
than the primary drug and toxic level has been reduced
in contrary to their primary drugs which has proved
hints for the future design of new derivatives with
higher potency and specificity.
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