Identification bioactive compounds from marine microorganism and exploration of structure–activity relationships (SARs)

Antimicrobial Drug ◽

Tertiary Amines ◽

Quaternary Amine ◽

Diverse Range ◽

Structure Activity

ABSTRACTMarine natural products (MNPs) have become new strong leads for antimicrobial drug discovery and an effective alternative to control drug resistant infections. Herein we report the bioassay guided fractionation of marine extracts from sponges Lendenfeldia, Ircinia and Dysidea that led us to identify novel compounds with antimicrobial properties. Tertiary amines or quaternary amine salts: anilines 1, benzylamines 2, tertiary amines 3 and 4, and quaternary amine salt 5, along with three known compounds (6-8) were isolated from a crude extract and MeOH eluent marine extracts. The absolute configurations of the new compounds were assigned based on tandem mass spectrometry (MS) analysis. Several of the compounds exhibited potent in-vitro antibacterial activity, especially against Methicillin-resistant Staphylococcus aureus (MRSA) (MICs from 15.6 to 62.5 micro g/mL). Herein, we also, report structure activity relationships of a diverse range of commercial structurally similar compounds. The structure activity relationships (SARs) results clearly demonstrate that modification of the amines through linear chain length, and inclusion of aromatic rings, modifies the observed antimicrobial activity towards different biological activity. Several commercially available compounds, which are structurally related to the molecules we discovered showed broad spectrum antimicrobial activity against different test pathogens with an MIC50 range of 50 to 0.01 microM. The results of cross-referencing antimicrobial activity and cytotoxicity establish that these compounds are promising potential lead molecules, with a favourable therapeutic index for antimicrobial drug development. Additionally, the SAR studies show that simplified analogues of the isolated compounds with increased bioactivity

Identification of Bioactive Compounds from Marine Natural Products and Exploration of Structure-Activity Relationships (SAR)

Antibiotics ◽

10.3390/antibiotics10030337 ◽

2021 ◽

Vol 10 (3) ◽

pp. 337

Author(s):

Mojdeh Dinarvand ◽

Malcolm Spain

Keyword(s):

Antimicrobial Activity ◽

Natural Products ◽

Drug Discovery ◽

Marine Natural Products ◽

Linear Chain ◽

Antimicrobial Drug ◽

Quaternary Amine ◽

Diverse Range ◽

Structure Activity

Marine natural products (MNPs) have been an important and rich source for antimicrobial drug discovery and an effective alternative to control drug resistant infections. Herein, we report bioassay guided fractionation of marine extracts from sponges Lendenfeldia, Ircinia and Dysidea that led us to identify novel compounds with antimicrobial properties. Tertiary amines or quaternary amine salts: aniline 1, benzylamine 2, tertiary amine 3 and 4, and quaternary amine salt 5, along with three known compounds (6–8) were isolated from a crude extract and MeOH eluent marine extracts. The antibiotic activities of the compounds, and their isolation as natural products have not been reported before. Using tandem mass spectrometry (MS) analysis, potential structures of the bioactive fractions were assigned, leading to the hit validation of potential compounds through synthesis, and commercially available compounds. This method is a novel strategy to overcome insufficient quantities of pure material (NPs) for drug discovery and development which is a big challenge for pharmaceutical companies. The antibacterial screening of the marine extracts has shown several of the compounds exhibited potent in-vitro antibacterial activity, especially against methicillin-resistant Staphylococcus aureus (MRSA) with minimum inhibitory concentration (MIC) values between 15.6 to 62.5 microg mL−1. Herein, we also report structure activity relationships of a diverse range of commercial structurally similar compounds. The structure-activity relationships (SAR) results demonstrate that modification of the amines through linear chain length, and inclusion of aromatic rings, modifies the observed antimicrobial activity. Several commercially available compounds, which are structurally related to the discovered molecules, showed broad-spectrum antimicrobial activity against different test pathogens with a MIC range of 50 to 0.01 µM. The results of cross-referencing antimicrobial activity and cytotoxicity establish that these compounds are promising potential molecules, with a favourable therapeutic index for antimicrobial drug development. Additionally, the SAR studies show that simplified analogues of the isolated compounds have increased bioactivity.

The Antimicrobial Activity of Cannabinoids

Antibiotics ◽

10.3390/antibiotics9070406 ◽

2020 ◽

Vol 9 (7) ◽

pp. 406

Author(s):

John A. Karas ◽

Labell J. M. Wong ◽

Olivia K. A. Paulin ◽

Amna C. Mazeh ◽

Maytham H. Hussein ◽

...

Keyword(s):

Antimicrobial Activity ◽

Natural Products ◽

Antimicrobial Agents ◽

Cannabis Sativa ◽

Herbaceous Plant ◽

Modes Of Action ◽

Structure Activity ◽

Rapid Emergence

A post-antibiotic world is fast becoming a reality, given the rapid emergence of pathogens that are resistant to current drugs. Therefore, there is an urgent need to discover new classes of potent antimicrobial agents with novel modes of action. Cannabis sativa is an herbaceous plant that has been used for millennia for medicinal and recreational purposes. Its bioactivity is largely due to a class of compounds known as cannabinoids. Recently, these natural products and their analogs have been screened for their antimicrobial properties, in the quest to discover new anti-infective agents. This paper seeks to review the research to date on cannabinoids in this context, including an analysis of structure–activity relationships. It is hoped that it will stimulate further interest in this important issue.

Antimicrobial Properties of Volatile Phenylpropanes

Natural Product Communications ◽

10.1177/1934578x1000500910 ◽

2010 ◽

Vol 5 (9) ◽

pp. 1934578X1000500 ◽

Cited By ~ 2

Author(s):

Alexander Pauli ◽

Karl-Heinz Kubeczka

Keyword(s):

Antimicrobial Activity ◽

Substitution Pattern ◽

Specific Effects ◽

Structure Activity ◽

Microbial Characteristics ◽

Cis And Trans Isomers ◽

Species Specific ◽

Cis And Trans

The examination of antimicrobial structure-activity relationships of 93 volatile phenylpropanes (VPs) and 21 related aromatic compounds revealed a dependence of antimicrobial activity from the kind and number of substituents on the aromatic ring, their substitution pattern and microbial characteristics, such as Gram coloring and strain specific factors. Eugenol isomers were predominantly inhibitory in a concentration range from 25 to 2000 mg/L against all microorganisms tested, which were three strains of Escherichia Coli and Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, Listeria monocytogenes, and Candida albicans. Etherified VPs were either less active or inactive depending on the type of side chain and/or substitution pattern. Differences in the antimicrobial activity of cis- and trans-isomers were observed. Species specific structure-activity relationships exist as was demonstrated with the Gram-negative bacteria (inactivity of E-ortho-eugenol) C. albicans (activity of di- and threefold methoxylated 1-propenylbenzenes), S. aureus and B. subtilis (activity of di-ortho methoxylated phenolic allylbenzenes and hydroquinone derivatives). With regard to the variety of observed specific effects and natural variation of susceptibility towards VPs according to literature reference data, the chances for successful prediction by computational analysis (QSAR) appear to be limited.

DESIGN, SYNTHESIS, AND PHARMACOLOGICAL EVALUATION OF SOME NOVEL BIS-THIAZOLE DERIVATIVES

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i4.23413 ◽

2018 ◽

Vol 11 (4) ◽

pp. 164 ◽

Cited By ~ 1

Author(s):

Ramesh M Borde ◽

Satish B Jadhav ◽

Rahul R Dhavse ◽

Achut S Munde

Keyword(s):

Antimicrobial Activity ◽

Hantzsch Reaction ◽

Thiazole Derivatives ◽

Design Synthesis ◽

Structure Activity ◽

Elemental Analyses ◽

And Staphylococcus Aureus ◽

Toxic Molecule

Objective: A series of substituted 5,2-bis-thiazoles derivatives were synthesized by Hantzsch reaction and evaluated in vitro for antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and Staphylococcus aureus. Methods: 2-(4-(benzyloxy)phenyl)-4-methylthiazole-5-carbothioamide were synthesized and allowed to react with various α-haloketones to give 5,2-bis-thiazoles, i.e., 2-(4-(benzyloxy)phenyl)-4-methyl-5-(4-substituted thiazol-2-yl)thiazole derivatives in excellent yield. The synthesized compounds were characterized by spectroscopic methods as well as elemental analyses. They were screened for their antimicrobial activity using the agar diffusion method.Result: Literature survey reveals that the synthesis of 2-(4-(benzyloxy)phenyl)-4-methyl-5-(4-substituted thiazol-2-yl)thiazole, i.e., (5,2-Bis-thiazoles) derivatives (10a-e) was not reported. The entire compound exhibited mild to moderate antimicrobial activity.Conclusion: The antimicrobial results revealed that the synthesized derivatives have significant antimicrobial properties, and further, structure– activity relationship studies may develop more potent and less toxic molecule.

1,5-Benzodiazepine derivatives as potential antimicrobial agents: design, synthesis, biological evaluation, and structure–activity relationships

Organic & Biomolecular Chemistry ◽

10.1039/c5ob00655d ◽

2015 ◽

Vol 13 (19) ◽

pp. 5497-5509 ◽

Cited By ~ 31

Author(s):

Lan-Zhi Wang ◽

Xiao-Qing Li ◽

Ying-Shuang An

Keyword(s):

Antimicrobial Activity ◽

Antimicrobial Agents ◽

Biological Evaluation ◽

Design Synthesis ◽

Structure Activity ◽

Benzodiazepine Derivatives

36 novel 1,5-benzodiazepine derivatives were synthesized and evaluated for their in vitro antimicrobial activity. The results revealed that most of the 1,5-benzodiazepine derivatives exhibited considerable potency against all of the tested strains.

Antimicrobial Screening, in Silico Studies and QSAR of Chalcone-based 1,4-disubstituted 1,2,3-triazole Hybrids

Drug Research ◽

10.1055/a-1296-7751 ◽

2020 ◽

Author(s):

Pinki Yadav ◽

Kashmiri Lal ◽

Ashwani Kumar

Keyword(s):

Topoisomerase Ii ◽

Qsar Model ◽

Quantitative Structure Activity Relationship ◽

Binding Modes ◽

E Coli ◽

Structure Activity ◽

In Silico Studies ◽

Microbial Strains

AbstractThe in vitro antimicrobial properties of some chalcones (1a–1c ) and chalcone tethred 1,4-disubstituted 1,2,3-triazoles (2a–2u) towards different microbial strains viz. Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Aspergillus niger and Candida albicans are reported. Compounds 2g and 2u exhibited better potency than the standard Fluconazole with MIC values of 0.0063 µmol/mL and 0.0068 µmol/mL, respectively. Furthermore, molecular docking was performed to investigate the binding modes of two potent compounds 2q and 2g with E. coli topoisomerase II DNA gyrase B and C. albicans lanosterol 14α-demethylase, respectively. Based on these results, a statistically significant quantitative structure activity relationship (QSAR) model was successfully summarized for antibacterial activity against B. subtilis.

An In Vitro Study on the Antimicrobial Properties of Essential Oil Modified Resin Composite against Oral Pathogens

Materials ◽

10.3390/ma13194383 ◽

2020 ◽

Vol 13 (19) ◽

pp. 4383

Author(s):

Barbara Lapinska ◽

Aleksandra Szram ◽

Beata Zarzycka ◽

Janina Grzegorczyk ◽

Louis Hardan ◽

...

Keyword(s):

Antimicrobial Activity ◽

Antibacterial Activity ◽

Antifungal Activity ◽

Antimicrobial Agents ◽

Resin Composite ◽

In Vitro Study ◽

Diffusion Method ◽

Oral Pathogens

Modifying the composition of dental restorative materials with antimicrobial agents might induce their antibacterial potential against cariogenic bacteria, e.g., S.mutans and L.acidophilus, as well as antifungal effect on C.albicans that are major oral pathogens. Essential oils (EOs) are widely known for antimicrobial activity and are successfully used in dental industry. The study aimed at evaluating antibacterial and antifungal activity of EOs and composite resin material (CR) modified with EO against oral pathogens. Ten EOs (i.e., anise, cinnamon, citronella, clove, geranium, lavender, limette, mint, rosemary thyme) were tested using agar diffusion method. Cinnamon and thyme EOs showed significantly highest antibacterial activity against S.mutans and L.acidophilus among all tested EOs. Anise and limette EOs showed no antibacterial activity against S.mutans. All tested EOs exhibited antifungal activity against C.albicans, whereas cinnamon EO showed significantly highest and limette EO significantly lowest activity. Next, 1, 2 or 5 µL of cinnamon EO was introduced into 2 g of CR and microbiologically tested. The modified CR showed higher antimicrobial activity in comparison to unmodified one. CR containing 2 µL of EO showed the best antimicrobial properties against S.mutans and C.albicans, while CR modified with 1 µL of EO showed the best antimicrobial properties against L.acidophilus.