SUMMARY & CONCLUSION

The credit of pyridine discovery goes to Anderson who first obtained it from
bone oil. Derivatives of Pyridine have been used in different applications like
medicine, used as anticancer, anti-hypertension, antifungal etc.
Different Derivatives of pyridine have been tested for various biological
activities. New derivatives are being synthesized by researchers across the
world. Success of a particular derivative for one activity can never be
predetermined let alone for multiple activities. QSAR can be a possible
approach to rationally obtain leads for synthetic chemists. These compounds can
be checked for suitability against different activities through extrapolation of
QSAR models on already synthesized derivatives.
QSAR is acronym for Quantitative Structure Activity Relationship (as
distinguished from QPAR and QSPR) is an attempt to mathematically relate
Biological Activity of certain compound to different quantitative properties of
the molecule. These may include easily calculated ones like molecular weight,
number of particular atom, groups etc to complex properties like electrostatic,
steric fields etc. These properties which are calculated are known as descriptors.
The increase in computing power over the last decade has led to a growth in
number of descriptors.

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Developing a QSAR model is essentially deriving a mathematical equation to

relate these descriptors to property under consideration. A group of analogous
compounds called as dataset is used as input for developing this equation.
These QSAR equations can be used as basis to predict activities of similar
compound. Descriptors being properties of the molecule can be calculated for
novel compounds also. By calculating the descriptors these novel compounds
can be checked for their probable activities via a vis multiple models
representing different activities.
Synthesis of any new compound without any direction is not very convenient
way because synthesis of any new compound requires a lot of time and lesser
amount of outcome. So, that with help of softwares predicted a new compound
leads to the QSAR study. In these study through various QSAR models and
approaches predicted 1,4 dihyropyridine derivatives .after the synthesis we
evaluate their biological activity and compare with the predicted activity.
This thesis divided into eight chapters.
Chapter-1
This chapter describes introduction of QSAR, history of QSAR, list of
descriptors, methologies, software as well as basic understanding of different
statistical parameter used in QSAR model development. This chapter also

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represent various part of QSAR, how to develop a model, descriptors with their
different type, feature selection, statistics, molecular modeling etc.
The whole overview on Quantitative Structure Activity Relationship in briefly
takes in this chapter.
Chapter-2
This chapter represent a review of literature consist of different QSAR studies
on different derivatives of 1,4 dihyropyridine. It also includes various historical
developments on QSAR studies. This chapter also presents different authors
views on these studies.

A survey of different synthetic methods of Hantzsch

reaction as well as other methods has to be taken. Step by step progresses

reported in QSAR field are described. Many types of software are used for
QSAR were integrated.
Chapter-3
This chapter describes the QSAR modeling on 31 compound of 3hyroxypyridine -4-one and 3-hyroxypyrane-4-one dataset with their known
minimum inhibitory concentration (MIC) biological activity determined on
s.aureus and c.albicans microorganism. These 31 compounds of dataset were
used for QSAR model development and developed around 50 models using
various different approaches like multiple linear regression, principal
component analysis, simulated annealing etc. around 299 physiochemical
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descriptors were used for these study. After that to find out the best QSAR
equation (correlation coefficient values) through the V-life software, this
equation is used for prediction of new compounds. For the prediction of new
compounds we substitute different alkyl, alkynes and functional groups on
different position of parent compound.
The predicted compounds were proposed for prospect study.
Chapter-4
A dataset of 1, 4 -dihyropyridine of 40 compounds and their calcium channel
antagonist activity determined on guinea pig ileum smooth muscles taken from
literature for QSAR modeling in this chapter.

Various descriptors show

different contribution for new QSAR equation. Between 50 models finally

discussed 4 models in this chapter.65 substitution was done on different
position of substituted phenyl ring .those compounds shows higher prediction
as compare to actual values were projected for further study.
Chapter-5
In this chapter qsar modeling was done on 31 compounds of given calcium
channel antagonist activity (IC50) .in this chapter substitution has to be done on
2, 3 and 4rth position of substituted phenyl ring of 1,4 dihyropyridine. Predicted
values were used for prediction of new compounds for the direction of nonsynthesized compounds.
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Chapter-6
This chapter describe the methodology of synthesis of 1,4-dihyropyridine
derivatives named as A1 to A4. Synthesis was done through Hantzsch single
step reaction. Synthesis of derivatives of 1,4 dihyropyridine using reaction
mixture of aldehyde,acetoacetate and ammonium hydroxide by condensation
method .
Chapter-7
In this chapter mentioned the spectral analysis of all synthesized derivatives of
1,4-dihyropyridine for their structure elucidation. it includes IR ,NMR and Mass
spectral analysis along with CHN analysis of all derivatives. The IR spectra of
compounds A1-A4 showed absorbtion band at 3418-3341 cm-1 due to the
presence of N-H stretching. The 1667-1690 cm-1, showed absorption band due to
the presence of keto group in the ester groups.
The 1HNMR spectra of compounds from A1 to A4 showed a singlet at 7.2 to
8.5 ppm trait to NH protons present in 1, 4-dihyropyridine ring. Another
important

singlet at 3.8 to 5.7 ppm, which was attributable to the C4-H

protons present in the 1, 4 dihyropyridine ring. Mass spectral analysis of all the
compounds showed molecular ion peaks, which confirmed the molecular mass
of those compounds.
Chapter-8
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In this chapter mentioned the experimental minimum inhibitory concentration

values of synthesized compounds. Values are evaluated against different kind of
micro-oraganism such as S.aureus, E.coli, P.aeroginosa and E.facelis. The
antibacterial assay was carried out through broth dilution method. All the
compounds experimental biological (MIC) activities were measured in
microgram/ml.
The predicted values (discussed in chapter 3) and experimental values were
compared for the development of new QSAR model. A new QSAR equation
were developed included with their descriptor contribution ,data fitness plot
and test set training set predicted vs experimental values graph.
The new QSAR equation showed better results as compare to past results.

CONCLUSION
In the present Quantitative structure activity relationship study developed more
than 100 models on different large data sets for 1,4 dihyropyridine derivatives.
After this study we concluded that
1) QSAR methodology is useful for pyridine derivatives. With the help of qsar
study on different large data sets gave more exploration and applicability to
pyridine derivatives.

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2) These study is very reliable for the prediction of new lead compounds. They
provide us a new way for non-synthesized compounds but at the same time it is
always required same biological activity data sets for the prediction.
3) It is not necessary that always QSAR model gives us same predicted and
experimental activity but if the trial and error process is continuously further
proceed. The new model shows very good prediction.
4) Present study represents a new effective QSAR equation for advance study of
different pyridine derivatives.
5)

QSAR models were generated through different approaches shows the

various comparable effectiveness on used data sets.

6) Different software made qsar study very fewer time consuming with less cost
and more productive with greater outcome as well as reduced the usage of
animal testing.
In short QSAR is the excellent tool for new drug discovery.

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