Antibacterial Screening Research Articles

Morpholine-modified Ru-based agents with multiple antibacterial mechanisms as metalloantibiotic candidates against Staphylococcus aureus infection.

Multidrug-resistant bacteria resulting from the abuse and overuse of antibiotics have become a huge crisis in global public health security. Therefore, it is urgently needed to develop new antibacterial drugs with unique mechanisms of action. As a versatile moiety, morpholine has been widely employed to enhance the potency of numerous bioactive molecules. In this study, a series of ruthenium-based antibacterial agents modified with the morpholine moiety were designed and characterized, aiming to obtain a promising metalloantibiotic with a multitarget mechanism. Antibacterial activity screening demonstrated that the most active complex Ru(ii)-3 exhibited the strongest potency against Staphylococcus aureus (S. aureus) with an MIC value of only 0.78 μg mL-1, which is better than most clinically used antibiotics. Notably, Ru(ii)-3 not only possessed excellent bactericidal efficacy, but could also overcome bacterial resistance. Importantly, Ru(ii)-3 very efficiently removed biofilms produced by bacteria, inhibited the secretion of bacterial exotoxins, and enhanced the activity of many existing antibiotics. The results of mechanism studies confirmed that Ru(ii)-3 could destroy the bacterial membrane and induce ROS production in bacteria. Furthermore, animal infection models confirmed that Ru(ii)-3 showed significant anti-infective activity in vivo. Overall, this work demonstrated that a morpholine-modified ruthenium-based agent is a promising antibiotic candidate in tackling the crisis of drug-resistant bacteria.

Repurposing the Antibacterial Activity of the Drug Teniposide Against Gram‐Positive Bacteria

Drug repurposing is sparking considerable interest due to reduced costs and development times. The current study details the screening of teniposide, an antitumor drug, for its antibacterial activity against both Gram‐positive and Gram‐negative strains, with a focus on Staphylococcus epidermidis (S. epidermidis), the primary causative agent of nosocomial and transplant‐related infections. The cytotoxicity was evaluated through 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) and hemolysis assays on immortalized human keratinocyte (HaCaT) cells and human erythrocytes. After 20 h of treatment, the recorded concentrations causing 50% cytotoxicity (CC50) and hemolysis (HC50) were 33.63 and 121.55 μg/mL, respectively. The antibacterial screening employed disk diffusion, the broth microdilution method, LIVE/DEAD staining, and a time‐killing test. The drug induced a growth inhibitory area in the 22–25 mm range for all Gram‐positive strains. The minimum concentration that inhibited 90% of bacteria (MIC90) was 6.25 μg/mL against Staphylococcus aureus and S. epidermidis and 12.5 μg/mL versus Enterococcus faecalis, exhibiting bactericidal action. Treatment resulted in S. epidermidis cell morphology deformities and damage to the cell membrane, observed by scanning electron microscopy (SEM). Mechanism analysis revealed alterations in the selective permeability of the cell membrane, observed under the fluorescence microscope by the absorption of propidium iodide (PI). The synergistic effect of teniposide in combination with fosfomycin and gentamicin was documented by disk diffusion and checkboard assay, recording a fractional inhibitory concentration index (FICI) of 0.28 and 0.37, respectively. The drug’s action on S. epidermidis biofilm biomass was investigated using crystal violet (CV) and MTT. Teniposide affected biofilm viability in a dose‐dependent manner, inducing, at a concentration of 3.12 μg/mL, a matrix inhibition of about 42% and 61%, with a sessile metabolic activity of 54% and 24% recorded after 2 and 24 h, respectively. Overall, this study suggests the potential repurposing of the anticancer drug teniposide as a therapeutic agent to counteract S. epidermidis infections.

Synthesis, Characterization and Antibacterial Properties of Complex [Ag(SCN)(2-NH2py)

The reaction of AgSCN with 2-aminopyridine in ammonia solution produces the colorless crystal of catena-poly [Ag(SCN))(C6H5N2)]n. The crystals were characterized by FTIR analysis and single crystal X-Ray diffraction. The silver(I) ion bind to one N atom of 2-aminopyridine, one N atom of thiocyanate and two S atoms of two thiocyanates to form a pseudo-tetrahedral complex. The presence of thiocyanates bridge ligand give an one-dimensional polymer. Complex [Ag(SCN)(2-NH2py)] crystallizes in monoclinic lattice and P21 space group with a=9,122(3) Å, b=4,1506(15) Å, c=11,269(4) Å, α= γ= 90°, β= 109,214(8)°, R= 0,0287. Intermolecular hydrogen bonds between amino group and thiocyanate NH-H…N-CS (2.389 Å) are also found in this structure. In vitro antibacterial screening complex was evaluated against two bacteria (Escherichia coli and Staphylococcus aureus). The results show that complex has higher antibacterial activity than 2-aminopyridine and KSCN. This is due to central ion and the ability of the ligand to interact with membrane proteins.

Combinatorial discovery of antibacterials via a feature-fusion based machine learning workflow.

The discovery of new antibacterials within the vast chemical space is crucial in combating drug-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). However, the traditional approach of screening the entire chemical library in an ergodic manner can be laborious and time-consuming. Machine learning-assisted screening of antibacterials alleviates the exploration effort but suffers from the lack of reliable and related datasets. To address these challenges, we devised a combinatorial library comprising over 110 000 candidates based on the Ugi reaction. A focused library was subsequently generated through uniform sampling of the entire library to narrow down the preliminary screening scale. A novel feature-fusion architecture called the latent space constraint neural network was developed which incorporated both fingerprint and physicochemical molecular descriptors to predict the antibacterial properties. This integration allowed the model to leverage the complementary information provided by these descriptors and improve the accuracy of predictions. Three lead compounds that demonstrated excellent efficacy against MRSA while alleviating drug resistance were identified. This workflow highlights the integration of machine learning with the combinatorial chemical library to expedite high-quality data collection and extensive data mining for antibacterial screening.

Evaluation of the Total Phenolic Content and Antimicrobial Activities of some Traditional Medicinal Plant

Aim: This study was aimed to scientifically prove the antimicrobial effect of the selected plants and to fulfil some of the recommendations of WHO, that research should be conducted on medicinal plants as alternative drugs for pathogenic bacteria and for possible elucidation of novel therapeutic preparations. Method: Total phenolic contents of the plant extracts (bulb extract of Allium sativum, bark extract of Alstonia scholaris, leaf extract of Amaranthus spinosus, leaf extract of Dysophylla auriculata and leaf extract of Murraya koenigii) were determined by using Folin-Ciocalteu method, and the values were expressed in microgram (µg) gallic acid equivalent (GAE) to 1 milligram (mg) of extract. The antibacterial activities of the 80% methanolic extracts of the plants were determined against five species of pathogenic bacteria; that were Listeria monocytogenes (ATCC 19115), Staphylococcus aureus (ATCC 700699) Escherichia coli 0157:H7, Salmonella paratyphi (ATCC 9150) and Salmonella typhi (ATCC 14028). Results: Out of the five selected samples, the highest phenolic content was recorded with the leaf extract of Murraya koenigii (64.97 ± 0.84). For the antibacterial screening, the most potent extract was observed with the leaf extract of Murraya koenigii against Staphylococcus aureus, with a minimum inhibitory concentration value of 15.63 µg/mL. Conclusion: The result obtained from this study confirmed the effectiveness of Murraya koenigii against the screened specie of bacteria. This work may be useful for the pharmaceutical industry in developing new natural product based therapy for pathogenic bacteria.

Vitex Negundo-Fe3O4-CuO green nanocatalyst (VN-Fe3O4-CuO): synthesis of pyrazolo[3,4-c]pyrazole derivatives via the cyclization of isoniazid with pyrazole and their antimicrobial activity, cytotoxicity, and molecular docking studies.

In this study, we developed a novel pyrazolo[3,4-c]pyrazole derivative with antibacterial and antifungal activities that shows great potential for treating infectious diseases. To evaluate the binding affinity of 1AJ0 and 1AI9 proteins for developing potent antibacterial and antifungal compounds, we used the Vitex negundo (VN) leaf extract as the capping and reducing agent and reacted it with Fe2O3 and Cu(OAc)2 solutions to synthesize the VN-Fe3O4-CuO nanocatalyst. The newly synthesized compounds were confirmed using Fourier transform infrared spectroscopy, transmission electron microscopy, UV-visible spectroscopy, and X-ray diffraction analyses. Antibacterial screening revealed that compound 1g was highly active against Escherichia coli (MIC: 1 μg mL-1) and was much more effective than the standard ciprofloxacin. Compound 1b showed a higher antifungal activity than clotrimazole against Candida albicans (MIC: 0.25 μg mL-1) and cytotoxic activity against MCF-7 cancer cell lines. Compounds 1a-1l were exhibited low cytotoxicity activity compared to the standard doxorubicin (LC50: 21.05 ± 0.82 μg mL-1). To further support the discovery of new active antibacterial agents, compounds 1g and 1b and proteins 1AJ0 and 1AI9 were examined using the AutoDock Vina program and were compared with the standards ciprofloxacin and clotrimazole. With the 1AJ0 protein, compound 1g had a higher docking score (-3.7 kcal mol-1) than ciprofloxacin (-5.6 kcal mol-1), and with the 1AI9 protein, compound 1b had a higher docking score (-4.8 kcal mol-1) than clotrimazole (-4.4 kcal mol-1). Additionally, molecular dynamics simulation was used to investigate the most probable binding mode of compounds 1b and 1g with 1AI9 and 1AJ0, respectively. The VN-Fe3O4-CuO catalyst was used to prepare pyrazolo[3,4-c]pyrazole derivatives, which were successfully characterized and screened for antimicrobial and cytotoxic activities, molecular docking, and molecular dynamics simulation studies.

Synthesis, Characterization and Anti-bacterial Screening of Fe(II) Mixed Ligand Complex of Ofloxacin with Ascorbic Acid

Aim: Mixed ligand complexes play a major role in biological processes by binding with small molecules and activating the enzymes for nuclease activity. This study is aimed at synthesizing, characterizing, and the antibacterial studies of 9-Fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H- Pyridol[1,2,3,-de]-1,4-benzoxazine-6-carboxylic acid (ofloxacin) and ascorbic acid metal complex. Methods: Iron(II) mixed ligand complex of ofloxacin and ascorbic acid was synthesized using the reflux method. The resulting complex, [Fe(Ofl)(Asc)] was characterized by its color, solubility, melting point, FTIR, electronic spectra, 1H NMR, and 13C NMR spectroscopy. Results: The dark gray color and the high melting point of the Fe(II) mixed ligand complex indicate that complexation occurred. From the electronic data, octahedral geometry was suggested for the complex. According to the FTIR data for both ofloxacin and ascorbic acid, the two ligands functioned as tridentate ligands, coordinating to the metal through the oxygen atoms of the two carbonyl groups, hydroxyl group in the case of ofloxacin and carbonyl, and the enolic C-2 and C-3 hydroxyl groups in the case of ascorbic acid. The antibacterial activities of the prepared mixed ligand complex were evaluated against Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis, and Escherichia coli. The result of the antibacterial activities of [Fe(Ofl)(Asc)] shows that the mixed ligand complex has higher antibacterial activities compared to the parent drug. In the mixed complex, the Fe(II) complex shows the highest inhibition against the four species. Conclusion: The complex exhibited more antimicrobial activity than the participating ligands. The results reported from this study will therefore aid in the development of more effective drugs that are effective against resistant microorganisms.

Correlation between Total Phenolic Content and Antibacterial Activities of Some Selected Traditional Plants against Some Species of Pathogenic Bacteria

Plants produce non-nutritive compounds known as secondary metabolites. These compounds can be found in several parts of the plants. Emphases have been placed on these compounds as curative agents in treating different types of diseases. Total phenolic contents of the plant extracts (leaf extract of Anacardium occidentalle, bulb extract of Allium sativum, bark extract of Casaurina equisetifolia, leaf extract of Dysophylla auriculata and bark extract of Mimusops elengi) were determined by using Folin-Ciocalteu method, and the values were expressed in microgram (µg) gallic acid equivalent (GAE) to 1 milligram (mg) of extract. The antibacterial activities of the 80% methanolic extracts of the plants were determined against nine species of pathogenic bacteria; that were Escherichia coli 0157:H7, Vibrio alginolyticus (ATCC 17749), Vibrio parahaemolyticus (ATCC 17082), Salmonella paratyphi (ATCC 9150), Yersiniae enterocolitica (ATCC 23715), Listeria monocytogenes (ATCC 19115), Salmonella typhi (ATCC 14028), Escherichia coli (ATCC 0157) and Staphylococcus aureus (ATCC 700699). Out of the five selected samples, the highest phenolic content was recorded with the bark extract of Mimusops elengi (442.59 ± 2.09). From the antibacterial screening, the most potent extract was observed with the bark extract of Mimusops elengi against L. monocytogenes (ATCC 19115), with a minimum inhibitory concentration value of 15.63 µg/mL, then followed by Allium sativum with 62.5 µg/mL. The correlation determined in this study between the total phenolic content and the antibacterial activity of the bark extract of Mimusops elengi confirmed its effectiveness against the screened species of bacteria. This work may be useful for the pharmaceutical industry in developing new natural product-based therapy for pathogenic bacteria.

Synthesis of Some Zinc and Copper Complexes of Benzimidazole

Two complexes of Cu(II) and Zn(II) ions with Benzimidazole ligand have been prepared. The ligand and its metal complexes have been characterized by using NMR and FTIR techniques. Ligand L acts as a bidentate ligand. The antibacteriall property of the complexes has been verified. The outcome of the antibacterial screening demonstrated that the complexes possess good biological activity against different bacterial strains. The results therefore suggest that all the complexes are better antifungal agents than the free ligand.

Phytochemical and antibacterial potential of lime (Citrus aurantifolia) and lemon (Citrus limon) juices as bioactivators of charcoal

Citrus juices are widely consumed because of their many health benefits and antimicrobial properties. Biological activators are preferred to the conventional chemical activators for safety and less health hazards thus the need to search for available indigenous biological materials for charcoal activation. Hence, the study on the potentials of lime (Citrus aurantifolia) and lemon (Citrus limon) juices as biological activators for charcoal. Freshly harvested lime and lemon juice were extracted using juice extractor and sterilized through filtration with membrane filter (0.45µl pore size). The phytochemical of the juices was determined and results revealed the presence of (carbohydrates, flavonoids, cardiac glycosides, saponins, terpenoids, ketose(fructose) and reducing sugars). The lime and lemon juices were subjected to antibacterial screening by agar well diffusion method against the test bacterial isolates (Staphylococcus aureus and Salmonella enterica subsp. entericaserovar) at 75%, 50%,25% and 12.5% concentrations respectively. The lime and lemon juice inhibition effects decreased with decrease in concentration. However, lime juice demonstrated higher inhibition across all concentrations in both test organisms with zones of inhibition (12-30mm) in Salmonella and (10-28 mm) in S. aureus while lemon juice demonstrated a low antibacterial activity across the different concentrations with zones of inhibition ranging from (12-17mm) in Salmonella and (9-24mm) in S. aureus. The phytochemical and antibacterial activities of lime and lemon juice revealed their potential utilization as bio activators.

PHYTOCHEMICAL SCREENING, ANTIBACTERIAL AND INSECTICIDAL ACTIVITIES OF STEM BARK EXTRACTS OF BOSWELLIA DALZIELII HUTCHIN FROM KALTUNGO, NIGERIA

The importance of traditional herbal medicinal system has now gained attention in developed and developing countries. Boswellia dalzielii is a tree grows in the wild usually in the Savannah region of West Africa. These work assessed the phytochemical constituents, antibacterial and insecticidal activities of the stem bark extracts of Boswellia dalzielii. The plant extracts were obtained using soxhlet method with petroleum ether, ethyl acetate, acetone, ethanol and water as solvents for 10 hours while the phytochemicals and insecticidal activities were determined using standard methods. The phytochemical screening showed significant presence of carbohydrate in the ethanol and water extracts while significant amount of tannin was detected only in the ethanol extract. The petroleum ether and ethyl acetate showed absence of carbohydrate, tannins, phlobotannin, cyanogenic glycoside, chlorogenic acid and alkaloid. Significant amount of flavonoid was seen in the water extract, while only the ethanolic extract showed significant amount of cardiac glycoside and alkaloid. The acetone extract showed significant quantity of alkaloid and terpenes and steroids. The antibacterial screening showed that ethanol extract had the highest inhibitory activity. The petroleum ether extract had the least active components with no activity on the test organisms. The insecticidal activity of the plant extracts showed that acetone extract had the highest insecticidal activity on both the test insects. Camponotus consobrinus shows the highest percentage mortality of 75% at a concentration of 500µg and LC50 of 1.64x102µg followed by the Acanthscelides obtectus with the percentage mortality of 53% at a concentration of 250µg and...

Review of: "Synthesis and Antibacterial Screening of Cefradine Schiff Bases and Their Metal Salts"

Review of: "Synthesis and Antibacterial Screening of Cefradine Schiff Bases and Their Metal Salts"

In silico and in vitro evaluation of newly synthesized pyrazolo-pyridine fused tetrazolo-pyrimidines derivatives as potential anticancer and antimicrobial agents

Diversely functionalized pyrazolo-pyridine fused tetrazolo-pyrimidines 10aa-am and 10ba-bn were successfully synthesized via a catalyst-free synthetic protocol with moderate to very good yields. The compounds were evaluated for cytotoxicity against MCF-7 and HEK-293 cells using MTT assay. Among the tested compounds, 10ab (IC50- 23.83 µM) and 10ah (IC50- 23.30 µM) demonstrated the highest potency against MCF-7 cells, while 10bc (IC50- 14.46 µM) and 10bh (IC50- 2.53 µM) exhibited excellent cytotoxicity against HEK-293 cells. Additionally, antibacterial screening was performed against three Gram-negative bacteria (E. coli, P. aeruginosa, and S. enterica) and three Gram-positive bacteria (S. aureus, B. megaterium, and B. subtilis) using broth dilution method, while antifungal activity was assessed against three fungal strains (A. niger, Penicillium, and S. cerevisiae) using agar well diffusion method. In antimicrobial screening, the majority of the compounds demonstrated significant antibacterial efficacy compared to antifungal activity. We also conducted comprehensive computational studies, including DFT calculations, molecular docking and dynamics, and drug-likeness assessments. In the DFT study, compounds 10ac and 10bc displayed stable conformations, indicating their potential for higher therapeutic activity. Molecular docking analyses revealed compelling interactions, with compound 10ah demonstrating docking score −7.42 kcal/mol against catalytical domain PARP1 (PDB ID: 7KK4) and 10bh exhibiting a best docking score −10.77 kcal/mol against human corticotropin-releasing factor receptor 1 (PDB ID: 4Z9G). A 100 ns molecular dynamics (MD) simulation study of compounds 10ah and 10bh revealed the stable conformation and binding energy in a stimulating environment. In drug-likeness assessments, both the compounds 10ah and 10bh adhere all the established guidelines. Communicated by Ramaswamy H. Sarma

Diversity of endophytic fungi isolated from tree spinach (Cnidoscolus aconitifolius) (Euphorbiaceae) and their bioactivities

Abstract. Praptiwi, Palupi KD, Ilyas M, Marlina L, Fathoni A. 2023. Diversity of endophytic fungi isolated from tree spinach Cnidoscolus aconitifolius (Euphorbiaceae) and their bioactivities. Biodiversitas 24: 6229-6239. Endophytic fungi associated with medicinal plants have been known as a reservoir for therapeutic compounds. Cnidoscolus aconitifolius I.M. Johns (Euphorbiaceae), which possesses several local names, including papaya jepang in Indonesia, has been historically used as traditional medicine. However, research on the bioactivity of endophytic fungi associated with it has yet to be conducted. The purposes of the study were to isolate endophytic fungi from C. aconitifolius and determine their bioactivity, i.e., antibacterial activity against Escherichia coli and S. aureus and free radical scavenging activity representing antioxidant activity. Identification of endophytic fungi was carried out based on their morphological characteristics. Total phenolic and flavonoid contents were determined by the spectrophotometric method. The qualitative antibacterial and antioxidant bioactivity screening was performed using the TLC-bioautography method. The quantitative analysis of antibacterial and antioxidant activity was conducted by microdilution to obtain IC50 and MIC values. In total, 14 endophytic fungal isolates were successfully isolated. Antioxidant analysis showed that one isolate had strong antioxidant activity, and one had moderate growth inhibition activity against E. coli. The total phenolic content strongly correlates with the AAI value as an indicator of antioxidant activity. The findings of this study reveal that Phomopsis PjBg-1, an endophytic fungus from C. aconitifolius, is identified as Phomopsis sp. LH243 possesses strong antioxidant activity and moderate antibacterial activity against E. coli. Endophytic fungi from C. aconitifolius have the prospect of being an alternative to antioxidants and antibacterials. The isolation of compounds responsible for bioactivities needs to be further studied.

Exploring the Antibacterial Potential of Semisynthetic Phytocannabinoid: Tetrahydrocannabidiol (THCBD) as a Potential Antibacterial Agent against Sensitive and Resistant Strains of Staphylococcus aureus.

Antimicrobial resistance (AMR) is one of the most challenging problems and is responsible for millions of deaths every year. We therefore urgently require new chemical entities with novel mechanisms of action. Phytocannabinoids have been adequately reported for the antimicrobial effect but not seriously pursued because of either stringent regulatory issues or poor drug-like properties. In this regard, the current work demonstrated the antibacterial potential of tetrahydrocannabidiol (THCBD, 4), a semisynthetic phytocannabinoid, against Staphylococcus aureus, the second-most widespread bug recognized by the WHO. THCBD (4) was generated from cannabidiol and subjected to extensive antibacterial screening. In in vitro studies, THCBD (4) demonstrated a potent MIC of 0.25 μg/mL against Gram-positive bacteria, S. aureus ATCC-29213. It is interesting to note that THCBD (4) has demonstrated strong effectiveness against efflux pump-overexpressing (SA-1199B, SA-K2191, SA-K2192, and Mupr-1) and multidrug-resistant (MRSA-15187) S. aureus strains. THCBD (4) has also shown a good effect in kill kinetic assays against ATCC-29213 and MRSA-15187. In the checkerboard assay, THCBD (4) has shown additive/indifference effects with several well-known clinically used antibiotics, tetracycline, mupirocin, penicillin G, and ciprofloxacin. THCBD (4) also exhibited good permeability in the artificial skin model. Most importantly, THCBD (4) has significantly reduced CFU in mice's in vivo skin infection models and also demonstrated decent plasma exposure with 16-17% oral bioavailability. Acute dermal toxicity of THCBD (4) suggests no marked treatment-related impact on gross pathophysiology. This attractive in vitro and in vivo profile of plant-based compounds opens a new direction for new-generation antibiotics and warrants further detailed investigation.

Exploring the Antimicrobial Potential of Pyrimidine Linked Hydrazinyl Azole Derivatives: Insights from Biological Assays and Molecular Docking Studies

AbstractWe present a study on a new class of Schiff bases with pyrimidine linked hydrazinyl azole backbone. These compounds were synthesized using conventional and ultrasonication methods. Our design strategy incorporated three heteroaromatic azoles and various substituents on the pyrimidine scaffold to enhance antimicrobial properties. Antibacterial and antifungal screenings were conducted against specific pathogens, and molecular docking studies supported the results. The compounds exhibited significant antimicrobial activities, particularly against K. pneumoniae, surpassing the standard drug. These Schiff bases hold promise as potential antimicrobial agents.

Novel amodiaquine analogues to treat cervical cancer and microbial infection in the future.

Aim: To synthesizeand explore the therapeutic potential of amodiaquine analogues. Methodology: New promising analogues weresynthesized by nucleophilic substitution at the 4-amino position and were characterized using 1H NMR, 13C NMRand FT-IR spectroscopic techniques. Results: Antibacterial and cytotoxic screening revealed the high potency of these compounds; analogue AS1 had an34.3±0.18mm zone of inhibition against Pseudomonas aeruginosa. Excellent activity against fungal strains, that is, Candida albicans (39.6±0.23mm) was shown by analogue AS2. Analogue AS1 had an IC50=4.2μg/ml against the HeLa cell line (cervical cancer) and binding energy against 5GWK (-8.32688kcal/mol), 1PFK (-6.4780kcal/mol) and 1TUP (-6.5279kcal/mol) in the docking study. Conclusion: The obtained results reveal that these analogues exhibit potent antimicrobial and cytotoxic potential.

Phytochemical and Antibacterial Screening of Chromolaena odorata Leaf Extract

The discovery of antibacterial drugs from natural sources as a substitute for preventing bacterial resistance has become necessary due to the increase in bacterial drug resistance. Chromolaena odorata has been reported to have antibacterial effects. Therefore, this study investigated the phytochemical components and antibacterial properties of C. odorata leaves. C. odorata leaves were collected, prepared, and extracted using a standard procedure with 95% methanol and 95% ethanol, respectively. Both extracts were subjected to phytochemical screening and Gas Chromatography-Mass Spectrometry to detect phytochemical compounds. Chromolaena odorata methanolic extract at a concentration of 50 mg/mL, 100 mg/mL, 150 mg/mL and 200 mg/mL was carried out for antibacterial screening using the agar well diffusion tested on Staphylococcus aureus (ATCC 43330), Bacillus subtilis (B29), Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 15442). The methanolic extract was present with tannin, terpenoid, alkaloid, and saponin while ethanolic extract was present with tannin and alkaloid. The GC-MS chromatogram identified as many as 27 and 19 compounds for ethanolic and methanolic extract, respectively. The C. odorata ethanolic extract consists mainly of Phenol (0.51%), Sesquiterpenoid (20.69%) and Fatty acid (39.2%). Meanwhile, C. odorata methanolic extract consists of Sesquiterpenoid (62.26%) and Fatty acid (17.11%). Antibacterial activity of S. aureus was the highest inhibition zone diameter with 7.67 mm to 10.33 mm from 50 mg/ml to 200 mg/mL concentration of C. odorata extract. Escherichia coli and B. subtilis inhibition zones diameter was 200 mg/mL concentration of C. odorata extract. No antibacterial activities were obtained for P. aeruginosa. This study suggests that C. odorata consists of a variety of phytochemicals and contains antibacterial properties. Thus, C. odorata represents a promising natural source for antibacterial resistance drugs.

New Pyrazole-Clubbed Pyrimidine or Pyrazoline Hybrids as Anti-Methicillin-Resistant Staphylococcus aureus Agents: Design, Synthesis, In Vitro and In Vivo Evaluation, and Molecular Modeling Simulation.

Two hybrid series of pyrazole-clubbed pyrimidines 5a-c and pyrazole-clubbed pyrazoline compounds 6a,b and 7 were designed as attractive scaffolds to be investigated in vitro and in vivo for antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. From the results of the in vitro antibacterial screening, compound 5c showed excellent activity (minimal inhibitory concentration, MIC = 521 μM) when compared with that of the reference antibiotic levofloxacin (MIC = 346 μM). The inhibition of the target dihydrofolate reductase (DHFR) enzyme by compounds 4 and 5a-c (IC50 = 5.00 ± 0.23, 4.20 ± 0.20, 4.10 ± 0.19, and 4.00 ± 0.18 μM, respectively) was found to be better than the reference drug trimethoprim (IC50 = 5.54 ± 0.28 μM). Molecular modeling simulation results have justified the order of activity of all the newly synthesized compounds as DHFR enzyme inhibitors, and compound 5c exhibited the best binding profile (-13.6169386 kcal/mol). Hence, the most potent inhibitor of the DHFR enzyme, 5c, was chosen to be evaluated in vivo for its activity in treating MRSA-induced keratitis in rats and that, in turn, significantly (P < 0.0001) reduced infection in rats when compared to MRSA-treated group results.

Docking study of novel designed indazole derivatives against topoisomerase-II DNA gyrase enzyme for antibacterial screening

Aim of the study was designed for the design of novel indazole derivatives and evaluation of their docking against topoisomerase-II DNA gyrase enzyme for the antibacterial screening. Different novel substituted indazol-3-yl benzenesulfonamide derivatives were designed for the synthesis from o-chlorobenzonitrile and phenyl hydrazine reaction and further, with benzene sulphonyl chloride reaction. These were evaluated for their docking targeting topoisomerase-II DNA gyrase enzyme for the antibacterial screening. A range of binding affinity (˗12.2 to ˗9.6 ​kcal/mol) was observed. Compound, 4-chloro-N-(1-phenyl-1H-indazol-3-yl)benzenesulfonamide had the highest binding affinity (˗12.2 ​kcal/mol) which is better than the standard norfloxacin (˗10.7 ​kcal/mol). Compounds (12a, 12c, 12e and 12g) with chloro-substitution at para position of sulfonamide had higher affinity as compared to the compounds (12b, 12d, 12f and 12h) with methyl substitution. A convenient method for the synthesis of indazole derivatives has been developed. 4-chloro-N-(1-phenyl-1H-indazol-3-yl)benzenesulfonamide had shown the best binding affinity. Further, more diverse bioactive moieties may be incorporated into indazole scaffold in the near future by future researchers and a great amount of effort may be dedicated to the exploration of medicinal approaches for their preparation and evaluation of their biological activities.