Current Topics in Medicinal Chemistry - Volume 23, Issue 20, 2023

Multi-drug resistance and its transmission is a ubiquitous health issue worldwide. The beta-lactamase AmpC resistance is a major concern among all health settings like hospitals and child care centers, etc. The clinical pipeline of the new antibiotics remains dry due to the production of AmpC beta-lactamases by the bacteria to develop resistance against antibiotics. According to the global antimicrobial resistance and use surveillance system, the rate of resistance to ciprofloxacin an antibiotic commonly used to treat urinary tract infections, varied from 8.4% to 92.9% for Escherichia coli and from 4.1% to 79.4% for Klebsiellapneumoniae in different countries. The lack of comprehensiveness within the data makes a choice problematic for the selection of appropriate β-lactam antibiotic for the treatment of resistant microorganisms. Most experts agree it is prudent to avoid expanded-spectrum (i.e. third-generation) cephalosporins for the treatment of organisms posing the greatest risk of AmpC induction. Nonetheless, the development of specific inhibitors for the AmpC enzyme, either naturally or synthetically, is only unfolding. To date, there is no single and clinically active drug available that inhibits the AmpC enzyme and combats multidrug resistance and its transmission in individuals. The deficit of the enzyme inhibitor focused the researchers to work in the area. This present review will emphasize on the chemistry, and structure of clinically important and potent inhibitors against AmpC enzymes.

GABA is an essential neurotransmitter in tissues other than the brain and has different functions. Cancer displays dysfunctional GABAergic system roles, comprising GAD, GABA, and GABA receptors. Both tumor-suppressing and carcinogenic characteristics of the GABAergic system have been reported in several malignancies. In the development of cancer cells, it plays oncogenesis- related roles. However, in some tumors, such as pancreatic cancer, it exhibits anti-cancer benefits in numerous human trials and animal models. As a result, GABAergic therapy may be used to treat cancer. The oxidative condition and the status of several malignant circumstances significantly influence the final GABAergic function in many tumors. Depending on the type of malignant tissue and other modifications, these roles manifest differently in malignancies. In this review, we, for the first time, concentrated on the oncogenic and tumor suppressor functions of GABA in various neoplasms, as well as its potential therapeutic implications. The significance of tumor suppressor function and the conditions that promote its function as a cancer genesis factor in cancer are discussed in this article.

Breast cancer is one of the main global diseases with a high mortality rate that mainly affects the female population. Despite the important advances that have been made concerning the treatments for this disease, research on less invasive therapies that generate fewer side effects for patients continues to develop. Consequently, researchers have turned their attention to using natural compounds (such as flavonoids) involved in molecular processes implicated in this type of cancer and are studying how these processes can be exploited to develop possible chemotherapies. This review offers a general description of studies on the antiproliferative activity of flavonoids obtained from natural sources for breast cancer treatment and their mechanism of action related to their structural characteristics. Reports were retrieved from electronic databases, such as Web of Science and Scopus using the following keywords: breast cancer, antiproliferative, flavonoids, and structureactivity. Articles published between 2015-2022 related to the topics mentioned above were selected, focusing on the flavonoids apigenin, luteolin, quercetin, and naringenin, as they are the ones with the highest activity and relevance according to the literature found.

Estrogen-related receptor alpha (ERRα), a member of the nuclear receptor superfamily, is strongly expressed in breast cancer cells. Its overexpression is associated with poor prognosis in triple- negative Breast Cancer (TNBC). ERRα expression could be inhibited by the downregulation of upstream oncogenic growth factors mTOR, HER2, and PI3K. Low expression of ERRα could suppress the migration and angiogenesis of tumor cells by inhibiting the activity of its downstream signals VEGF and WNT11. Studies have confirmed that ERRα inverse agonists can inhibit ERRα expression to treat breast cancer. Inverse agonists of ERRα could disrupt the interactions of ERRα with its coactivators and inhibit tumor development. Existing ERRα inverse agonists have shown moderate efficacy in inhibiting the growth of breast cancer cells. Clinical inverse agonists of ERRα have not been found in the literature. This review focuses on the research progress and the structureactivity relationship of ERRα inverse agonists, providing guidance for the research and discovery of new anti-tumor compounds for TNBC.

Alpinia malaccensis, commonly known as “Malacca ginger” and “Rankihiriya,” is an important medicinal plant of Zingiberaceae. It is native to Indonesia and Malaysia and widely distributed in countries including Northeast India, China, Peninsular Malaysia and Java. Due to vide pharmacological values, it is necessary to recognize this species for its significance of pharmacological importance. This article provides the botanical characteristics, chemical compounds of vegetation, ethnopharmacological values, therapeutic properties, along with the potential pesticidal properties of this important medicinal plant. The information in this article was gathered by searching the online journals in the databases such as PubMed, Scopus, Web of Science etc. The terms such as Alpinia malaccensis, Malacca ginger, Rankihiriya, pharmacology, chemical composition, ethnopharmacology, etc., were used in different combinations. A detailed study of the available resources for A. malaccensis confirmed its native and distribution, traditional values, chemical properties, and medicinal values. Its essential oils and extracts are the reservoir of a wide range of important chemical constituents. Traditionally, it is being used to treat nausea, vomiting and wounds along with as a seasoning agent in meat processing and as perfume. Apart from traditional values, it has been reported for several pharmacological activities such as antioxidant, antimicrobial, anti-inflammatory etc. We believe that this review will help to provide the collective information of A. malaccensis to further explore it in the prevention and treatment of various diseases and help to the systematic study of this plant to utilize its potential in various areas of human welfare.

Nonribosomal peptide synthetases, consisted of multiple catalytic domains, are involved in the biosynthesis of an important family of bioactive natural products in a coordinated manner. Among the functional domains, adenylation domains are specifically responsible for recognizing carboxylic acid building blocks and synthesizing aminoacyl adenylates. Given their critical roles in the biosynthesis of the growing peptide, A-domains are also referred to as the “gatekeeper”. In this review, very recent developments on the A-domains from NRPSs are reviewed to expand the fundamental knowledge of the A domain, including knowledge on the structures, functions, and molecular interactions. Several recent examples were also discussed to highlight the great potential of A-domain engineering. This study should provide a framework for the combinatorial biosynthesis or synthetic biology-driven microbial production of novel nonribosomal peptides.

Aptamers, as artificially synthesized short nucleotide sequences, have been widely used in protein analysis, gene engineering, and molecular diagnostics. Currently, the screening process of aptamers still relies on the traditional SELEX process, which is cumbersome and complex. Moreover, the success rate of aptamer screening through the SELEX process is not high, which has become a major challenge. In recent years, the development of computers has facilitated virtual screening, which can greatly accelerate the screening process of aptamers through computer-assisted screening. However, the accuracy and precision of current virtual screening software on the market vary. Therefore, this work summarizes the docking characteristics of four mainstream molecular docking software programs, including Auto dock, Auto dock Vina, MOE, and hex Dock, in recent years. Moreover, the accuracy and prediction performance of these four molecular docking software programs for aptamer docking based on experimental data is also evaluated. This will guide researchers in the selection of molecular docking software. Additionally, this review provides a detailed overview of the application of computer-aided virtual screening in aptamer screening, thus providing a direction for future development in this field.