Special Issue (September)
Online - 2455-3891
Print - 0974-2441
International Conference of Pharmacy (ICP-2017) at School of Pharmaceutical Sciences, Lovely Professional University, Punjab, India
PREDICTION OF ACTIVITY SPECTRA OF SUBSTANCES ASSISTED PREDICTION OF BIOLOGICAL
ACTIVITY SPECTRA OF POTENTIAL ANTI-ALZHEIMER’S PHYTOCONSTITUENTS
ABHINAV ANAND, NEHA SHARMA, NAVNEET KHURANA*
Department of Pharmacology, School of Pharmaceutical Sciences, Lovely Professional University, Punjab, India.
Email: navi.pharmacist@gmail.com
Results: Several phytoconstituents were predicted to have effects better than marketed drugs under some or the other out of the chosen six
areas of pharmacological intervention. On the other hand, several new avenues were predicted in which the in vitro and in vivo evaluation of the
phytoconstituents can be made on the basis of PASS predicted activities.
Conclusion: PASS is an important tool for virtually screening the compounds of interest for the biological activities of interest. This helps the
researchers to streamline the research. However, PASS has its own share of limitations amidst a multitude of merits.
Keywords: Alzheimer’s disease, Prediction of activity spectra of substances, Phytoconstituents, Prediction.
INTRODUCTION
Alzheimer’s disease (AD) has been recognized as the most prevalent
form of dementia among geriatric persons since the commencement
of 21
st
century. Over 47.5 million people globally were estimated to be
living with dementia in 2016. By 2030, the figure is being speculated to
rise to 75.6 million [1]. AD is a neurodegenerative disorder that generally
appears in mid-to-late adulthood. It is associated with a progressive
and rather irreversible decline in memory various other cognitive
capabilities. In AD, there is neuronal destruction and deterioration of
neural connections in the cerebral cortex region of the brain along with
a substantial loss of brain mass [2]. AD is invariably progressive and
lethal within 5-10 years of its onset [3]. Death usually ensues due to
complications of the chronic illness. It is one of the top five most common
causes of mortality in population of the United States [4]. In some rare
cases, it appears in people in their 40 seconds and 50 seconds, but
otherwise it is a disease of old age. Based on clinical, population-based
studies, about 200,000 people under 65 years of age are suffering from
AD. In contrast, around 5 million of those over 65 years of age have AD.
As per speculations, a new case of AD is expected to be developed every
33 seconds, by 2050 [5].
AD is characterized by the presence of two neuropathological
hallmarks, i.e., extracellular amyloid beta plaques (Aβ) and intracellular
Tau neurofibrillary tangles (NFTs). The plaques constitute chiefly of the
neurotoxic peptide amyloid, which forms after the sequential cleavage
of a large precursor protein, i.e., amyloid precursor protein (APP) by
two enzymes, namely, β-secretase and γ-secretase. However, Aβ is not
formed if APP is first acted upon and cleaved by the enzyme α-secretase
instead of β-secretase. NFTs comprise mainly of the protein tau. In the
development of AD, Tau uncouples from microtubules and aggregates
into tangles thereby inhibiting transport and resulting in microtubule
disassembly. It also depends on the phosphorylation of Tau (Fig. 1) [6].
The current pharmacotherapeutic approaches for AD provide only
symptomatic relief. There is an urgent need for discovery and
development of new drugs that could halt or delay the progression
of disease by treating the underlying causes [7,8]. The new drug
development is a very tedious process and is associated with high
probability of negative results in terms of pharmacological efficacy. In
such a scenario, it becomes imperative that a tool should be available
which could predict the pharmacological properties beforehand.
It would enable the researchers to streamline the research more
efficiently. Prediction of activity spectra of substances (PASS) is such
a tool which can predict the pharmacological properties beforehand
and would help in screening pharmacological potential leads for a
particular condition [9].
The applicability of PASS to phytoconstituents has been exhibited
in earlier investigations [12-14]. The current version of PASS is
capable of predicting over 3750 biological effects, biochemical
modes of action, specific toxicities, and metabolic terms based on
2D structures or canonical simplified molecular-input line-entry
system (SMILES) with a mean accuracy of almost 95%. It predicts
Full Proceeding Paper
Received: 14 July 2017, Revised and Accepted: 25 July 2017
ABSTRACT
Methods: Several phytoconstituents were selected on the basis of reported literature. The anti-AD activities of selected phytoconstituents were
predicted by employing canonical simplified molecular-input line-entry system obtained from PubChem using PASS online.
Objective: To predict the biological activity of certain phytoconstituents for their anti-AD effects.
Objective: Alzheimer’s disease (AD) is a neurodegenerative disorder that is associated with loss of memory and cognition. It is responsible for
60-80% of dementia cases. The current pharmacotherapy provides only symptomatic relief. There is an urgent need for discovery and development
of newer drugs that could delay or halt the progression of disease. Prediction of activity spectra of substances (PASS) is a valuable interface
that should be adopted as a quintessential tool for predicting potential anti-AD capability of molecules.
Plant sources have been an integral part of traditional medicine systems
since ages, be it the Traditional Indian Medicine System or Traditional
Chinese Medicine System. Around 70% of New Chemical Entities which
later became drugs between the periods of 1981-2006
originated from plant sources [10]. Screening of molecules virtually
is of specific importance to form basis of pharmacology and
receptor interactions for phytoconstituents [11].
© 2017 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.
org/licenses/by/4. 0/) DOI: http://dx.doi.org/10.22159/ajpcr.2017.v10is4 .21330