Current Organic Chemistry - Volume 25, Issue 6, 2021

Azole frameworks serve as privileged scaffolds in the contemporary drug design paradigm owing to their unique physicochemical profile that promotes the development of highly selective, physiological benevolent chemotherapeutics. Several azole nuclei function as bioisostere in medicinal chemistry and prompt the development of tailored therapeutics for targeting the desired biological entities. Besides, the azole scaffold forms an integral part in the advanced drug designing methodologies, such as target template insitu drug synthesis, that assists in rapid identification of the hit molecules form a diverse pool of leads; and direct biomolecule-drug conjugation, along with bioorthogonal strategies that ensure localization, and superior target specificity of the directed therapeutic. Lastly, the structural diversity of azole framework and high yielding click synthetic methods provide a comprehensive Structure-Activity Relationship analysis for design optimization of the potential drug molecules by fine-tuning the placement of different substituents critical for the activity. This review provides a comprehensive analysis of the synthesis and anticancer potential of azole based chemotherapeutics.

Cancer is characterized by an uncontrolled proliferation of cells, dedifferentiation, invasiveness and metastasis. Endothelial growth factor (eGF), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF), Fibroblast growth factor (FGF), Vascular endothelial growth factor (VEGF), checkpoint kinase 1 & 2 ( Chk1 & Chk2), aurora kinases, topoisomerases, histone deacetylators (HDAC), poly(ADP-Ribose)polymerase (PARP), farnesyl transferases, RAS-MAPK pathway and PI3K-Akt-mTOR pathway, are some of the prominent mediators implicated in the proliferation of tumor cells. Huge artillery of natural and synthetic compounds as anticancer, which act by inhibiting one or more of the enzymes and/or pathways responsible for the progression of tumor cells, is reported in the literature. The major limitations of anticancer agents used in clinics as well as of those under development in literature are normal cell toxicity and other side effects due to lack of specificity. Hence, medicinal chemists across the globe have been working for decades to develop potent and safe anticancer agents from natural sources as well as from different classes of heterocycles. Benzimidazole is one of the most important and explored heteronucelus because of their versatility in biological actions as well as synthetic applications in medicinal chemistry. The structural similarity of amino derivatives of benzimidazole with purines makes it a fascinating nucleus for the development of anticancer, antimicrobial and anti-HIV agents. This review article is an attempt to critically analyze various reports on benzimidazole derivatives acting on different targets to act as anticancer so as to understand the structural requirements around benzimidazole nucleus for each target and enable medicinal chemists to promote rational development of antitumor agents.

The heterocyclic compounds have a great significance in medicinal chemistry because they have extensive biological activities. Cancer is globally the leading cause of death and it is a challenge to develop appropriate treatment for the management of cancer. Continuous efforts are being made to find a suitable medicinal agent for cancer therapy. Nitrogencontaining heterocycles have received noteworthy attention due to their wide and distinctive pharmacological activities. One of the most important nitrogen-containing heterocycles in medicinal chemistry is ‘quinazoline’ that possesses a wide spectrum of biological properties. This scaffold is an important pharmacophore and is considered a privileged structure. Various substituted quinazolines displayed anticancer activity against different types of cancer. This review highlights the recent advances in quinazoline based molecules as anticancer agents. Several in-vitro and in-vivo models used along with the results are also included. A subpart briefing natural quinazoline containing anticancer compounds is also incorporated in the review.

Heterocyclic are a class of compounds that are intricately entwined into life processes. Almost more than 90% of marketed drugs carry heterocycles. Synthetic chemistry, in turn, allocates a cornucopia of heterocycles. Among the heterocycles, indole, a bicyclic structure consisting of a six-membered benzene ring fused to a five-membered pyrrole ring with numerous pharmacophores that generate a library of various lead molecules. Due to its profound pharmacological profile, indole got wider attention around the globe to explore it fully in the interest of mankind. The current review covers recent advancements on indole in the design of various anti-cancer agents acting by targeting various enzymes or receptors, including (HDACs), sirtuins, PIM kinases, DNA topoisomerases, and σ receptors.

Flavonoids are polyphenolic compounds that are mainly derived from fruits and vegetables and constitute an essential part of plant-derived beverages such as green tea, wine and cocoa-based products. They have been shown to possess anticancer effects via different mechanisms such as carcinogen inactivation, antiproliferation, cell cycle arrest, induction of apoptosis and differentiation, inhibition of angiogenesis, anti-oxidation and reversal of multidrug resistance or a combination of any two or more of these mechanisms. The present review summarizes the chemistry, biosynthesis and anticancer evaluation of flavonoids in both animal and human studies. A special emphasis has been placed on the flavonoids that are being screened in different phases of clinical trials for chemoprotective action against various cancers.

Some thiophenic derivatives show important biological activity or are used as intermediates in organic synthesis. For this reason, it is very important to develop new synthesis procedures with good yields and using few synthesis steps. The present work offers an overview of the method for obtaining substituted thiophenes reported in the literature, and the synthetic procedures used from push-pull systems. In this work, we present the synthesis of 14 new tetrasubstituted thiophenes starting from amino mercaptoacrylates and α-brominated acetamides, derived from furoyl and benzoylacetonitrile, respectively. Best yields (66 to 85%) were obtained through ultrasonic irradiation. Combined use of spectroscopic methods and elementary analysis was done for characterization of all the compounds.