Key Heterocyclic Cores for Smart Anticancer Drug–Design Part I

The variety of natural compounds is indispensable due to their mechanism of action. For many years, natural compounds have been used to develop new classes of chemotherapeutic agents. Chemotherapeutic agents derived and synthesised from natural sources could be the best possible alternatives to minimise the harmful aftereffects of conventionally used agents against cancer, especially oral and maxillofacial carcinoma and tumors. The proposed chapter concentrates on recent research on various classes of natural scaffolds and their analogues that possess potent antitumor activity. Moreover, we would like to provide an analysis of preclinical and/or clinically investigated natural compounds. These compounds and their synthetic heterocyclic analogues were found to be obtained through bioactivity and mechanism of actiondirected isolation and characterization, conjoined with modification using rational drug design-based approaches and analogue synthesis. Structure-activity relationships, structural change, and molecular mechanisms of action will all be examined.

The human population is affected by the wide range of malignant cancers. Several cancer treatment options, including surgery, radiation, chemotherapy, immunotherapy, and others, are available or within our reach. However, the excessive toxic effects that assimilate the negative impact on patients and thus impede progress in cancer treatment have yet to be identified. Recent efforts in the research and development of anticancer drugs derived from natural products have led to the identification of numerous heterocyclic terpenes that inhibit cell proliferation, metastasis, apoptosis, and other mechanisms. The anticancer activity of the terpenoids is quite promising, and it could lead to more opportunities for cancer therapy. The current chapter provides an overview of recent developments in the field of heterocyclic terpenes and their analogues as anticancer compounds. As a result, this provides an overview of the progress made in developing terpenes and analogues as potential anticancer agents, including their synthetic modification, SAR, and action mechanisms. The current studies are hoped to help researchers in increasing their chances of gaining breakthrough insights in the field that can be used in cancer therapeutic practise.

Cancer is known as a silent killer that wreaks havoc on our immune systems. Cancer is the leading cause of death in the majority of cases. Resistance to anticancer drugs is becoming more agile, which encourages researchers to develop more effective cancer therapies. Heterocyclic compounds have long been important in advanced medicinal chemistry. Among the various heterocyclic scaffolds, benzothiazole (BT) is one of the most privileged moieties with a diverse range of biological activities such as anticancer, antidiabetic, anti-inflammatory, antiviral, antifungal, and so on. A large number of novel benzothiazole derivatives have been synthesized. Some of the mechanisms used by BT to treat cancer include tyrosine-kinase inhibitors, topoisomerase II inhibitors, CYP450 enzyme inhibitors, Abl kinase inhibitors, tubulin polymerase inhibitors, and HSP90 inhibitors. In this chapter, we will discuss various benzothiazole-hybrid compounds that optimise potency as well as anticancer activity in a concise manner. The goal of this chapter is to highlight recent research on benzothiazole scaffolds and their anticancer activity against various biological targets. The chapter will also provide updates on benzothiazole-containing drugs that are currently in clinical trials as well as those that have recently been granted patents. 

Cancer, caused by uncontrolled cell growth in any part of the body, is a significant life-threatening burden for the growing civilization. Though cancer research has reached a high level, considering the high cost of the available therapies to treat various cancers, the morbidity and mortality rates are still high. Organ toxicity, lack of cell specificity, drug resistance, and short half-life with adverse side effects are the major hurdles associated with currently used therapeutics. Therefore, there is a high need to search for new anticancer agents with minimal side effects and toxicity. In this connection, nature always acts as a treasury for scientists by offering its natural sources to fight the war against various life-harvesting diseases. Nowadays, hybrid molecule drug designs attract much attention among organic and medicinal chemists. What is more interesting about the hybrid molecule is that, depending upon the target diseasecreating protein, scientists are designing and optimising the target molecule by considering their structure-activity relationship studies (SARs). Among the different natural sources, quinoline, quinolone, and their hybrid derivatives are the most privileged ones. They are found as the central core of many bioactive natural products as well as drug molecules (camptothecin, bosutinib, cabozantinib, pelitinib, lenvatinib, levofloxacin, voreloxin, ciprofloxacin, garenofloxacin, etc.) acting as anticancer agents. Literature is enriched with the excellent achievements of hybrid quinoline and quinolone derivatives which function as anticancer agents through various mechanisms such as Bcl-2 inhibition, ALDH inhibition, kinase inhibition, topo-II, and EGFR-TK inhibition, etc. Given the excellent performance of quinoline and quinolone hybrid derivatives, it will be worthwhile to continue researching them. 

Heterocyclic compounds play an important role in drug design and discovery, and they have been used to treat a variety of diseases, including cancer. Cancer is one of the leading causes of death in the world. However, various drugs and therapies are available on the market. The novel synthetic drugs show promising invitro activity, but the route to clinical trials is hampered by their low bioavailability and rapid metabolism. Tetrazoles have gained a lot of attention in recent years because they have the broadest biological activity spectrum of any heterocycle. Tetrazoles are a type of nitrogen heterocycle that has been found to be active in a variety of natural products as well as the biologically active nucleus. A vast number of studies have demonstrated the importance of this moiety in medicinal chemistry. The tetrazole ring has a similar structure to carboxylic acids and functions as a bioisostere analogue. A bioisostere is a group of molecules that have similar physiological properties, including biological activity. Tetrazole derivatives have been shown to have anti-hypertension, anti-fungal, anti-malarial, anti-leishmaniasis, anti-diabetic, anti-cancer, and a variety of other biological activities. The tetrazole moiety functions as a good pharmacophore in the drug design and discovery fields, particularly in terms of rational drug design with high efficiency with structure and anti-cancer activity.

 Cancer, which is spreading throughout the world, is quickly becoming the leading cause of major fatalities. The most difficult task for global researchers today is to develop anticancer leads with minimal side effects. Heterocyclic chemistry is an important and unique class of medicinal chemistry as a large number of drugs being used in chemotherapy have a heterocyclic ring as their basic structure, in spite of various side effects. Because of the presence of heteroatoms such as oxygen, nitrogen, and sulphur, heterocyclic compounds can be used as hydrogen bond donors and acceptors. As a result, they can more effectively bind to pharmacological targets and receptors via intermolecular hydrogen bonds, resulting in pharmacological effects. They can also change the liposolubility and thus the aqueous solubility of drug molecules, resulting in remarkable pharmacotherapeutic properties. Medicinal chemists are concentrating on anticancer agents based on heterocyclic compounds. The goal of this chapter is to attempt to compile a dataset of advances in various nitrogen and oxygen-containing heterocyclic rings with anticancer activities from 2017 to 2020. The chapter covered the most recent research on novel anticancer heterocyclic derivatives, as well as the structure-activity relationship (SAR). The chapter provides the reader with advanced knowledge of the strategies required for designing nitrogen- and oxygen-containing heterocyclic compounds as anticancer agents.