Month 2016
Synthesis of Novel Triazole-incorporated Isatin Derivatives as Antifungal, Antitu-
bercular, and Antioxidant Agents and Molecular Docking Study
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amino acid sequence of enzyme was obtained, and from
Protein Data Bank using Blast search, homologous
sequence was obtained. Based on the result of blast search,
we used the crystal structure of human lanosterol
14α-demethylase (CYP51) with azole as a template for
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of amino acid sequence of CA-CYP51 (P10613) and
human CYP51 (3LD6_B) was performed. The parameters
like sequence identities and sequence positives are
important for the selection of template structure. The
sequence identities and sequence positives were found to be
39 and 54%, which satisfy the basic criteria for comparative
modeling (Figure S1, Supporting Information). The quality
of generated C. albicans lanosterol 14α-demethylase model
was assessed by using the well-validated program likes
PROCHECK [31], and its structural validation is shown in
Figure S2 (Supporting Information). It was found that
residue were followed, 82.45% in core region, 11.42% in
allowed region, and 4.44% in generously allowed region.
The only 1.69% residues were found in disallowed region.
The further structural superimposition was performed to
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mean-square deviation value was found within a standard
range of 0.997607 Å. The validation study of the model
suggested that it was perfect for further computation study.
Absorption, distribution, metabolism, and excretion
prediction. All the synthesized compounds 8, 9a–g, and
10a–b were evaluated by computational study for prediction
of ADME properties. In this computational study, we have
calculated topological polar surface area (TPSA), number of
rotatable bonds, molecular volume, molecular weight,
logarithm of partition coefficient (miLog P), number of
hydrogen bond acceptors, number of hydrogen bond
donors, and Lipinski’s rule of five using Molinspiration
online property calculation toolkit. Percentage ABS was
calculated as follows: % ABS=109 ꢀ(0.345×TPSA).
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Acknowledgments. The authors M.H.S. and D.D.S. are very
much grateful to the Council of Scientific and Industrial Research
(CSIR), New Delhi, for the award of Senior Research Fellowship.
Authors are also thankful to the Head, Department of Chemistry,
Dr. Babasaheb Ambedkar Marathwada University, Aurangabad,
for providing laboratory facility.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet