Book Volume 3
Alkaloids: A Brief Overview of Botanical and Pharmacological Properties
Page: 1-43 (43)
Author: Claudio Ferrante* and Luigi Menghini
DOI: 10.2174/9789815123678123030004
PDF Price: $30
Abstract
The classical definition of alkaloids describes this class of secondary
metabolites as chemical structures containing nitrogen as part of a heterocyclic, with
alkaline character, characterized by complex structure and limited distribution, mainly
in the plant kingdom. The modern history of alkaloids starts in the early nineteenth
century as figured by two milestone dates, 1803 when Derosne described the isolation
of a mixture containing narcotin and morphine from opium, and 1819 when the chemist
Meissner delivered an operative definition of the term alkaloid. They have been
observed with sporadic distribution in bacteria, fungi, Pteridophytae and Gymnophytae,
while they are mainly represented in higher plants and within Angiosperms,
particularly in selected families, such as Annonaceae, Lauraceae, Loganaceae,
Menispermaceae, Papaveraceae, Ranuncolaceae, Rubiaceae, Rutaceae, Solanaceae and
others. Frequently, a plant activates selectively a metabolic pathway that produces a
mixture of multiple but structure-related alkaloids. Sometimes, dozens may be with a
restricted number representing the majority of the total content. The latter parameter
could change significantly as a result of a plethora of many factors, including the plant
organ, seasonal variations, phenological status and others. As general rules, the
alkaloids are segregated in the form of salt inside cell vacuole or sometimes in laticifer,
mainly through the superficial tissues, supporting the hypothesis of their biological
involvement in plant-environment interactions.
Synthesis of Natural Morphinans and Development of Related Alkaloids
Page: 44-71 (28)
Author: Andrea Angeli*
DOI: 10.2174/9789815123678123030005
PDF Price: $30
Abstract
Morphine, an alkaloid isolated from the opium poppy, has been widely used
as an analgesic, and has been a fascinating synthetic target of organic chemists. All
these opioid drugs produce their biological actions through three receptor types, µ, δ,
and κ, belonging to the G-protein-coupled receptor family. Currently, used opioid
analgesics also share a number of severe side effects, limiting their clinical usefulness.
The chemically highly versatile structure of morphine and its related natural alkaloids
has continuously engaged the interest of pharmaceutical and medicinal chemistry
research, aiming for the synthesis and identification of numerous semi- and synthetic
opioid ligands as safer therapeutic agents or with novel therapeutic properties and with
lesser unwanted side effects with the final goal to reduce complications and to improve
patient compliance. This review provides the first total synthesis reported in 1952 and
focuses on representative examples of various derivatives and interesting approaches
for the development of structurally correlated molecules with substitutions at different
rings position leading to preclinical and clinically valuable opioids.
Caffeine-based Compounds for the Treatment of Neurodegenerative Disorders
Page: 72-99 (28)
Author: Mattia Spano* and Giacomo Di Matteo
DOI: 10.2174/9789815123678123030006
PDF Price: $30
Abstract
Neurodegenerative disorders, such as Alzheimer’s and Parkinson’s, are very
complex diseases, whose treatment and prevention are still very problematic to date.
The search for new potential treatments is always a current topic. In this context, the
discovery of molecules with a dual-targeting action against both MAO-B enzyme and
A2A receptor has been largely pursued in recent years, considering their involvement in
the etiological process of these diseases. In particular, caffeine, an alkaloid largely
present in beverages and foods, has been shown to possess beneficial effects in the
prevention/treatment of neurodegenerative disorders. Moreover, in vitro assays have
confirmed its interaction with the MAO-B enzyme and A2A receptor, stimulating the
synthesis of caffeine chemical derivatives that can strongly act against these two
targets. In this chapter, several classes of caffeine derivatives have been discussed, with
particular attention on their synthesis and (dual) biological activity of MAO-B enzyme
and A2A receptor.
Piperine Derivatives: New Trends in Medicinal Chemistry
Page: 100-127 (28)
Author: Adriana Trifan*, Özlen Güzel-Akdemir and Simone Carradori
DOI: 10.2174/9789815123678123030007
PDF Price: $30
Abstract
The alkaloid piperine has always attracted the interest of pharmaceutical
botanists for its biological activities and pharmacokinetics-modulating properties. It is
currently used in combination with other compounds for the treatment of several
diseases. Starting from its peculiar structure, medicinal chemists have explored the
chemical space around the amide portion, the conjugated double bond chain and the
benzodioxole ring. This approach led to a large plethora of derivatives, which
diversified the properties of the parent compound or improved its potency against
specific targets or biological systems. In this chapter, several classes of piperine
derivatives have been discussed and classified according to the proposed therapeutic
use, with a particular attention on their structure-activity relationships and biological
activity values.
Designing Noscapine-based Anti-Cancer Agents
Page: 128-151 (24)
Author: Paulo F. Silva Santos-Júnior, Igor J. S. Nascimento and Edeildo F. Silva-Júnior*
DOI: 10.2174/9789815123678123030008
PDF Price: $30
Abstract
Cancer is the second leading cause of death globally, in which factors, such
as tobacco, radiation, and obesity contribute to this alarming data. Among the available
pharmacotherapy, natural products, such as noscapine, have historical evidence in
treating this disease, showing promising results aimed at inhibiting tubulin. In this
context, this remarkable molecule has been tested as a conjugated drug in treating the
COVID-19 pandemic. In this chapter, we demonstrate noscapine structurally-related
compounds, analyzing them based on SAR studies, and discuss the most promising
results reported so far.
Biogenic Amine and Amino Acid Derivatives as Carbonic Anhydrase Modulators
Page: 152-188 (37)
Author: Emanuela Berrino* and Fabrizio Carta
DOI: 10.2174/9789815123678123030009
PDF Price: $30
Abstract
Biogenic amines (BAs) and amino acids (AAs) are essential components of
every living organism, being the precursors of vital compounds, such as hormones,
alkaloids, nucleic acids and proteins, among others. They are directly involved in many
metabolic processes, growth regulation, cellular transmission and diseases. A plethora
of biological substrates yet to be fully identified are the targets of BAs and AAs. The
Carbonic Anhydrases (CAs; EC 4.2.1.1) are listed among them. These metalloenzymes
are virtually expressed in every living organism, with eight genetically distinct families
described to date. CAs main biological function is represented by CO2
hydration
catalysis. Amino acids and amines are usually reported as efficient CA activators and
are thus potentially useful for therapeutic purposes in aging and neurodegenerative
diseases as well as tissue engineering. To date, polyamines are the only exception as
they were identified to act as CA inhibitors. Here, we will review the main
contributions in the field covering the effects of such crucial molecules on CAs
expressed in various organisms (mammals, fungi, protozoan, bacteria and archaea).
Synthetic analogues of amines and amino acids obtained from various drug design
approaches, will also be considered.
Design of Antimalarial Compounds on Quinoline Scaffold: From Plant to Drug
Page: 189-237 (49)
Author: Paulo F. S. Santos-Júnior, Igor J. S. Nascimento, Geraldo J. S. Neto, Rafael J. M. Omena, Thiago M. Aquino, João X. Araújo-Júnior, Mario R. Meneghetti and Edeildo F. Silva-Júnior*
DOI: 10.2174/9789815123678123030010
PDF Price: $30
Abstract
Plasmodium species are responsible for a high incidence of cases and
resistance, even with several approved drugs. Quinoline derivatives are recognized as a
source of active compounds, where tafenoquine has been recently approved. Cases of
resistance and the indiscriminate use of anti-malarials against COVID-19 have
negatively contributed to eradicating this disease. In this context, modifications at 2- or
4-amino positions from the quinoline scaffold or even its metal complexes have shown
promising advances in the field, especially against resistant strains, such as 3D7, W2,
D10, Dd2, K1
, and FCR-3. In this chapter, we discussed all aspects involving such
compounds, presenting their results based on SAR analysis and recent
contributions/advances involving this classic scaffold arising from nature.
Introduction
Medicinal chemists around the world have been inspired by nature and have successfully extracted chemicals from plants. Research on enzymatic modifications of naturally occurring compounds has played a critical role in the search for biologically active molecules to treat diseases. This book set explores compounds of interest to researchers and clinicians. It presents a comprehensive analysis about the medicinal chemistry (drug design, structure-activity relationships, permeability data, cytotoxicity, appropriate statistical procedures, molecular modelling studies) of different compounds. Each chapter brings contributions from known scientists explaining experimental results which can be translated into clinical practice. Volume 3 presents (1) a brief overview of botanical and pharmacological properties of alkaloids, (2) a summary of the synthesis of natural morphinans and related alkaloids, (3) caffeine-based compounds for the treatment of neurodegenerative disorders, (4) piperine derivatives, (5) noscapine-based anti-cancer agents, (6) biogenic amines and amino acid derivatives as carbonic anhydrase modulators and (7) antimalarial compounds on quinoline scaffolds. The objective of this book is to fulfil gaps in current knowledge with updated information from recent years. It serves as a guide for academic and professional researchers and clinicians.