The 10 most-cited articles in Archiv der Pharmazie, 2020

The human immunodeficiency virus type 1 (HIV-1) is the major etiological agent responsible for the acquired immunodeficiency syndrome (AIDS), which is a serious infectious disease and remains one of the most prevalent problems at present. Currently, combined antiretroviral therapy is the primary modality for the treatment and management of HIV/AIDS, but the long-term use can result in major drawbacks such as the development of multidrug-resistant viruses and multiple side effects. 1,2,3-Triazole is the common framework in the development of new drugs, and its derivatives have the potential to inhibit various HIV-1 enzymes such as reverse transcriptase, integrase, and protease, consequently possessing a potential anti-HIV-1 activity. This review covers the recent advances regarding the 1,2,3-triazole hybrids with potential anti-HIV-1 activity; it focuses on the chemical structures, structure-activity relationship, and mechanisms of action, covering articles published from 2010 to 2020.

Infections caused by Gram-positive and -negative bacteria are one of the foremost causes of morbidity and mortality globally. Antibiotics are the mainstay of therapy for bacterial infections, but the emergence and wide spread of drug-resistant pathogens have already become a huge issue for public healthcare systems. The coumarin moiety, which is ubiquitous in nature, could bind to the B subunit of DNA gyrase in bacteria and inhibit DNA supercoiling by blocking the ATPase activity; hence, coumarin derivatives possess potential antibacterial activity. Several coumarin-containing hybrids such as coumermycin A1, clorobiocin, and novobiocin have already been used in clinical practice for the treatment of various bacterial infections; thus, it is conceivable that hybridization of the coumarin moiety with other antibacterial pharmacophores may provide opportunities for the development of novel antibiotics. This review outlines the advances in coumarin-containing hybrids with antibacterial potential in the recent 5 years and the structure-activity relationships are also discussed.

The isatin framework is a useful template for the development of novel anticancer agents. This is exemplified by the fact that several isatin-based anticancer agents, such as semaxanib, sunitinib, nintedanib, and hesperadin, are already in use or under clinical trials for the treatment of diverse kinds of cancers. Isatin-based hybrids could be obtained by incorporating other anticancer pharmacophores into the isatin skeleton and they have the potential to overcome drug resistance with reduced side effects. Thus, isatin-based hybrids may provide attractive scaffolds for the development of novel anticancer agents. This review covers the recent advances of isatin-based hybrids with anticancer activity, covering articles published between 2001 and 2019. The anticancer activities of these molecules and the structure-activity relationships are also discussed. The purpose of this review article is to set up the direction for the design and development of isatin-based hybrids with high efficacy and low toxicity.

Cancer can invade or spread to almost all parts of the body. The increasing morbidity and high mortality of cancer create a great demand for the development of novel anticancer drugs. Coumarin derivatives are ubiquitous in nature and can readily interact with diverse enzymes and receptors in cancer cells via weak bond interactions; hence, coumarin is a highly privileged pharmacophore for the development of novel anticancer agents. This review will focus on the recent development of coumarin hybrids as potential anticancer agents covering articles published from 2019 to 2020.

Alkaline phosphatases are found in different living species and play crucial roles in various significant functions, such as hydrolyzing a variable spectrum of phosphate-containing physiological compounds, contributing to DNA synthesis, bone calcification, and attenuation of inflammation. They are homodimeric enzymes; each subunit contains one magnesium ion and two zinc ions crucial for the catalytic activity of the enzyme. Alkaline phosphatases exist in four distinct isoenzymes (placental, intestinal, germ cell, and tissue nonspecific alkaline phosphatases), which are expressed by four different genes; each one of them has distinguished functions. Any disturbance in the gene expression of alkaline phosphatase eventually induces serious disease conditions. Thus, the need to explore new lead inhibitors has increased recently. In this literature review, we aim to investigate the role of alkaline phosphatase in different diseases and physiological conditions and to study the structure-activity relationships of recently reported inhibitors. We focused on the lead compounds reported in…

Postmenopausal women are at high risk of developing breast cancer due to estrogen production in peripheral tissues of the body other than ovaries. Aromatase is present in breast tissue, leading to local estrogen production which can be inhibited by a variety of steroidal and nonsteroidal aromatase inhibitors. There are many aromatase inhibitors available in clinical practice like exemestane, formestane, anastrozole, letrozole, fadrozole, vorozole, and so forth, but the major challenge in anti-breast cancer therapy is the toxicity associated with aromatase inhibitors, especially the steroidal class of drugs. It is, therefore, urgently required to develop novel anticancer drugs having better safety and efficacy for the treatment of breast cancer. This study highlights the aromatase inhibitors reported in the current literature as well as the recent advances in the management of breast cancer.

As the growth in resistance to bacterial infection treatments poses a grave threat to global health in the 21st century, there is a constant need to explore novel antibacterial agents that have the ability to overcome drug resistance. Indole-containing alkaloids are widely distributed in nature, and a variety of indole-containing alkaloids have already been applied in clinical practice, proving that indole-containing alkaloids are fascinating and privileged scaffolds for the development of novel drugs. Moreover, indole-containing alkaloids could exert their antibacterial activity through the inhibition of efflux pumps, the biofilm, filamentous temperature-sensitive protein Z, and methicillin-resistant Staphylococcus aureus pyruvate kinase; so, indole-containing alkaloids constitute an important source of novel antibacterial agents. This review is an endeavor to highlight the advances in the development of indole-containing alkaloids with antibacterial potential, covering articles published in the recent 10 years.

Although most of the heterocycles have been reported to possess a significant pharmacological activity, only a few of them, namely quinoline derivatives, have exhibited the finest biological activities. Despite the few medicinal properties of the plain quinoline molecule, its derivatives exhibit diverse pharmacological properties such as anticancer, anti-inflammatory, antibacterial, antiviral, antifungal, antiprotozoal activities, and so on. The potential antimicrobial properties of the quinoline derivatives are evident from the decades of research on these derivatives. Owing to limitations like drug resistance, high cost, severe side effects, and less bioavailability of previously synthesized antimicrobial agents, these drugs have become obsolete in recent years. Hence, the design of more efficient antimicrobial drugs must be given topmost priority. A breakthrough in drug discovery is a must to prevent malevolent microbial diseases. Addressing all these issues, researchers have been continuously contributing to antimicrobial drug discovery. Herein, a short description of the…

Abstract Alzheimer's disease (AD) is a neurodegenerative disorder characterized by dementia, memory impairment, cognitive dysfunction, and speech impairment. The utility of cholinergic replacement by acetylcholinesterase (AChE) inhibitors in AD treatment has been well documented so far. Recently, studies have also evidenced that human carbonic anhydrases (hCAs) serve as an important target for AD treatment. In this direction, the improvement of new multitarget drugs, which can simultaneously modulate several mechanisms or targets included in the AD pathway, may be a potent strategy to treat AD. In light of these data for understanding and developing AD‐related multitarget AChE and hCAs inhibitors, in this study, novel methylene‐aminobenzoic acid and tetrahydroisoquinolynyl‐benzoic acid derivatives ( 4a – g and 6a – g ) were designed. The synthesized analogs were experimentally validated for their effects by in vitro and direct enzymatic tests. Also, the compounds were subjected to in silico monitoring with Schrödinger Suite software to assign binding affinities of potential…

Abstract Coumarins and their derivatives are receiving increasing attention due to numerous biochemical and pharmacological applications. In this study, a series of novel coumarin–1,2,3‐triazole‐acetamide hybrids was tested against some metabolic enzymes including α‐glycosidase (α‐Gly), α‐amylase (α‐Amy), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), human carbonic anhydrase I (hCA I), and hCA II. The new coumarin–1,2,3‐triazole‐acetamide hybrids showed K i values in the range of 483.50–1,243.04 nM against hCA I, 508.55–1,284.36 nM against hCA II, 24.85–132.85 nM against AChE, 27.17–1,104.36 nM against BChE, 590.42–1,104.36 nM against α‐Gly, and 55.38–128.63 nM against α‐Amy. The novel coumarin–1,2,3‐triazole‐acetamide hybrids had effective inhibition profiles against all tested metabolic enzymes. Also, due to the enzyme inhibitory effects of the new hybrids, they are potential drug candidates to treat diseases such as epilepsy, glaucoma, type‐2 diabetes mellitus (T2DM), Alzheimer's disease (AD), and leukemia. Additionally, these inhibition effects were compared with…