Antibiotic-resistant bacteria pose a global health threat. Traditional antibiotics can lose their effectiveness, and the development of novel effective antimicrobials has become a priority in recent years. In this area, plants represent an invaluable source of antimicrobial compounds with vast therapeutic potential. To review the full possible spectrum of plant antimicrobial agents (plant compounds, extracts and essential oils) discovered from 2016 to 2021 and their potential to decrease bacterial resistance. Their activities against bacteria, with special emphasis on multidrug resistant bacteria, mechanisms of action, possible combinations with traditional antibiotics, roles in current medicine and future perspectives are discussed. Studies focusing on the antimicrobial activity of compounds of plant origin and their mechanism of action against bacteria were identified and summarized, including contributions from January 2016 until January 2021. Articles were extracted from the Medline database using PubMed search engine with relevant keywords and operators. The search yielded 11,689 articles from 149 countries, of which 101 articles were included in this review. Reports from 41 phytochemicals belonging to 20 families were included. Reports from plant extracts and essential oils from 39 plant species belonging to 17 families were also included. Polyphenols and terpenes were the most active phytochemicals studied, either alone or as a part of plant extracts or essential oils. Plasma membrane disruption was the most common mechanism of antimicrobial action. Number and position of phenolic hydroxyl groups, double bonds, delocalized electrons and conjugation with sugars in the case of flavonoids seemed to be crucial for antimicrobial capacity. Combinations of phytochemicals with beta-lactam antibiotics were the most studied, and the inhibition of efflux pumps was the most common synergistic mechanism. In recent years, terpenes, flavones, flavonols and some alkaloids and phenylpropanoids, either isolated or as a part of extracts, have shown promising antimicrobial activity, being membrane disruption their most common mechanism. However, their utilization as appropriate antimicrobials need to be boosted by means of new omics technologies and network pharmacology to find the most effective combinations among them or in combination with antibiotics.

Background: Multi-drug-resistant bacteria such as Methicillin-Resistant Staphylococcus aureus (MRSA) disseminate rapidly amongst patients in healthcare facilities and suppose an increasingly important cause of community-associated infections and associated mortality. The development of effective therapeutic options against resistant bacteria is a public health priority. Plant polyphenols are structurally diverse compounds that have been used for centuries for medicinal purposes, including infections treatment and possess, not only antimicrobial activity, but also antioxidant, anti-inflammatory and anticancer activities among others. Based on the existing evidence on the polyphenols’ antibacterial capacity, polyphenols may be postulated as an alternative or complementary therapy for infectious diseases.Objective: To review the antimicrobial activity of plant polyphenols against Gram-positive bacteria, especially against S. aureus and its resistant strains. Determine the main bacterial molecular targets of polyphenols and their potential mechanism of action.Methodology: The most relevant reports on plant polyphenols’ antibacterial activity and their putative molecular targets were studied. We also performed virtual screening of thousand different polyphenols against proteins involved in the peptidoglycan biosynthesis to find potential valuable bioactive compounds. The bibliographic information used in this review was obtained from MEDLINE via PubMed.Results: Several polyphenols: phenolic acids, flavonoids (especially flavonols), tannins, lignans, stilbenes and combinations of these in botanical mixtures, have exhibited significant antibacterial activity against resistant and non-resistant Gram-positive bacteria at low μg/mL range MIC values. Their mechanism of action is quite diverse, targeting cell wall, lipid membrane, membrane receptors and ion channels, bacteria metabolites and biofilm formation. Synergic effects were also demonstrated for some combinations of polyphenols and antibiotics.Conclusion: Plant polyphenols mean a promising source of antibacterial agents, either alone or in combination with existing antibiotics, for the development of new antibiotic therapies.

Drug-resistant bacteria pose a serious threat to human health worldwide. Current antibiotics are losing efficacy and new antimicrobial agents are urgently needed. Living organisms are an invaluable source of antimicrobial compounds. The antimicrobial activity of the most representative natural products of animal, bacterial, fungal and plant origin are reviewed in this paper. Their activity against drug-resistant bacteria, their mechanisms of action, the possible development of resistance against them, their role in current medicine and their future perspectives are discussed. Electronic databases such as PubMed, Scopus and ScienceDirect were used to search scientific contributions until September 2020, using relevant keywords. Natural compounds of heterogeneous origins have been shown to possess antimicrobial capabilities, including against antibiotic-resistant bacteria. The most commonly found mechanisms of antimicrobial action are related to protein biosynthesis and alteration of cell walls and membranes. Various natural compounds, especially phytochemicals, have shown synergistic capacity with antibiotics. There is little literature on the development of specific resistance mechanisms against natural antimicrobial compounds. New technologies such as -omics, network pharmacology and informatics have the potential to identify and characterize new natural antimicrobial compounds in the future. This knowledge may be useful for the development of future therapeutic strategies.

Marine secondary metabolites are a promising source of unexploited drugs that have a wide structural diversity and have shown a variety of biological activities. These compounds are produced in response to the harsh and competitive conditions that occur in the marine environment. Invertebrates are considered to be among the groups with the richest biodiversity. To date, a significant number of marine natural products (MNPs) have been established as antineoplastic drugs. This review gives an overview of MNPs, both in research or clinical stages, from diverse organisms that were reported as being active or potentially active in cancer treatment in the past seventeen years (from January 2000 until April 2017) and describes their putative mechanisms of action. The structural diversity of MNPs is also highlighted and compared with the small-molecule anticancer drugs in clinical use. In addition, this review examines the use of virtual screening for MNP-based drug discovery and reveals that classical approaches for the selection of drug candidates based on ADMET (absorption, distribution, metabolism, excretion, and toxicity) filtering may miss potential anticancer lead compounds. Finally, we introduce a novel and publically accessible chemical library of MNPs for virtual screening purposes.