2352 Thorat et al.
Asian J. Chem.
decreasing order of the glide energy of 3-methyl-1-benzofuran-
2-carbohydrazide with PBDs in the decreasing order as 1RJB
> 1TE6 > 3LAU > 1VOM > 4BBG > 2BOU > 3V3M > 3FDN
> 3MK2.
The above docking images [electrostatic interactions (blue)]
shows that two amino acids in all proteins as ARG and LYS
shows positive interactions. 3-Methyl-1-benzofuran-2-carbo-
hydrazide shows stronger such interaction with same amino
acids of 4BBG, 3V3M, 3MK2 and 1VOM indicates that
orientation of the molecule does not change during docking
in major extend by the changing of skeleton or functional
group. But such type of interaction is weaker in 3LAU, 3FDN
and 2BOU whereas is absent with 1RJB and 3V3M.
such as LYS and ARG, both containing amino groups which
get protonated and forming quaternary ammonium cation
which get interact with π-electrons of aromatic rings. The polar
hydroxyl group (hydrogen having partial positive charge/
oxygen having partial negative charge/lone pair of electrons of
oxygen) interact with aromatic ring. These type of interactions
are depends on the orientation of the molecule in the docking
site and amino acid arrangement in the same. The 1TE6 and
3MK2 PDBs are shows weak interaction with 3-methyl-1-
benzofuran-2-carbohydrazide which can be explained by their
low docking score.
The antimycobacterium activity of hydrazide should be
assessed against M. tuberculosis using micro plate alamar
blue assay (MABA). The standard or reference used for the
antituberculosis study are pyrazinamide, streptomycin and
ciprofloxacin and their standard values for the antituberculosis
test which was performed her are - 3.125 µg/mL, 6.25 µg/mL
and 3.125 µg/mL respectively while that of target compound
is 6.25 µg/mL.
The above docking images [electrostatic interactions
(pink)] shows that two amino acids in all proteins as ASP and
GLU shows negative interactions. This type interaction depends
on the number of positive charge centre present in the ligand
molecules and number of donor amino acids present in the
docking site. 1RJB, 4BBG, 1TE6 and 3MK2 PDBs shows
maximum number of such type of interactions with 3-methyl-
1-benzofuran-2-carbohydrazide while these interactions are
weaker with 3FDN, 3LAU, 2BOU, 1VOM and 3V3M.
Glide lipo explains the lipophilic and lipophobic attraction
between ligand and amino acid residue at the docking site
after recombination. The molecule is undissociated and thus
available for penetration through various lipid barriers. The
rate of penetration is strongly depends on the lipophilicity of
the drug molecule in its unionized form. The lipophilic-hydro-
philic balance plays very important role in passive transport
and active transport along with drug metabolism. As length of
hydrophobic chain increases, both partion coefficient and
anaesthetic potency increases. Lipophilic and phobic attraction
between 3-methyl-1-benzofuran-2-carbohydrazide and amino
acid residue at the docking site in the order of 3LAU > 1VOM
> 3MK2 > 1RJB > 3V3M > 3FDN > 2BOU > 4BBG PDBs at
the neutral pH = 7. At lower pH, hydrazide get protonated and
its lipophilicity character goes on decreasing. The hydrazide
shows weaker lipophilic and hydrophobic attraction in 1TE6.
The electron rich π-system (containing electron donating
group) are generally interact with other electron deficient π-
system having electron withdrawing group. These are denoted
by green colour and are called as hydrophobic interactions.
Also, electron rich π-centre interacts with cation (denoted by
dark blue colour) and electron deficient centre interact with
anion (denoted by pink colour). The 3-methyl-1-benzofuran-
2-carbohydrazide shows the π-π interactions with the amino
acid residue containing aromatic ring or π-electrons, the amino
acids such as ARG (C=N bond) and PHE, HIE and HID
(aromatic ring) shows such interactions with it. The π-cation
interaction are shown by those amino acid residue containing
free cation or partial positive charge centre in their side chain
ACKNOWLEDGEMENTS
The authors are grateful to Schrödinger Software Organi-
zation and Cresset Software Organization for their support.
REFERENCES
1. P.K. Mahakhud and M.R. Parthasarathy, Indian J. Chem., 34B, 713 (1995);
B.R. Thorat, D. Shelke, R.G. Atram and R.S. Yamgar, Heterocycl. Lett.,
3, 385 (2013).
2. G. Samuelsson, Drugs of Natural Origin, Swedish Pharmaceutical,
Stockholm (1992); B.R. Thorat, D. Shelke, R.G.Atram and R.S.Yamgar,
Heterocycl. Lett., 3, 331 (2013); B.R. Thorat, S. Shelke, R. Jagtap and
R.S. Yamgar, Heterocycl. Lett., 4, 321 (2014).
3. J.W. Mason, N. Eng. J. Med., 316, 455 (1987).
4. G.N. Walker and R.T. Smith, J. Org. Chem., 36, 305 (1971).
5. M. Mandewale, B.R. Thorat, B. Nazirkar, V.B. Thorat, A. Nagarsekar
and R.S. Yamgar, J. Chem. Sci., 110, 279 (2016).
6. R. Madhu and M.D. Karvekar, Int. J. Pharm. Pharm. Sci., 2, 6466 (2010).
7. G. Parameshwarappa, B. Raga, S.O. Khandre and S.S. Sangapure,
Heterocycl. Commun., 15, 335 (2009).
8. A.R. Leach, Molecular Modelling: Principles and Applications, Pearson
Education EMA, edn 2 (2001); B.R. Thorat, R. Jagtap, V.B. Thorat, A.
Khemanar and R.S.Yamgar, Heterocycl. Lett., 5, 59 (2015); B.R. Thorat,
R. Jagtap, V.B. Thorat, A. Khemanar and R.S. Yamgar, Int. J. Comput.
Bioinfo. In Silico Model, 4, 597 (2015); B.R. Thorat, R. Jagtap, V.B.
Thorat, A. Khemanar and R.S. Yamgar, Der Pharma Chemica, 7, 169
(2015); B.R. Thorat, R. Jagatap, A.S. Nagarsekar,V.B. Thorat and R.S.
Yamgar, J. Adv. Bioinformatics Appl. Res., 6, 62 (2015).
9. E.M. Gordon M.A. Gallop and D.V. Patel, Acc. Chem. Res., 29, 144
(1996).
10. P.B. Fernandes, Curr. Opin. Chem. Biol., 2, 597 (1998).
11. R.P. Hertzberg and A.J. Pope, Curr. Opin. Chem. Biol., 4, 445 (2000).
12. D.E. Clark, Ann. Rep. Comput. Chem., 1, 133 (2005).
13. B.R. Thorat, M. Mandewale, S. Shelke, P. Kamat, R.G. Atram, M.
Bhalerao and R. Yamgar, J. Chem. Pharm. Res., 4, 14 (2012).
14. B. Thorat, V. Ahuja, M. Mandewale, R. Yamgar and L.V. Gavali, World
J. Pharm. Res., 4, 2250 (2015).