Compounds 4g Research Articles

Synthesis and Characterization of New 5-Fluoroisatin-Chalcone Conjugates with Expected Antimicrobial Activity

Pathogenic microorganisms are becoming more and more resistant to antimicrobial agents. So the synthesis of new antimicrobial agents is very important. In this work, new 5-fluoroisatin-chalcone conjugates 5(a–g) were synthesized based on previous research that showed the modifications of the isatin moiety led to the synthesis of many derivatives that have antimicrobial activity. 4-aminoacetophenone reacts with 5-fluoroisatin to form Schiff base (3), which in turn reacts with two different groups of aromatic (carbocyclic and heterocyclic) aldehydes 4(a–g) separately to form the final compounds 5(a–g). Proton-nuclear magnetic resonance (¹H-NMR) and Fourier-transform infrared (FT-IR) spectroscopy were used to confirm the chemical structures of the newly prepared compounds. Finally, the final compounds, 5-fluoroisatin-chalcone conjugates 5(a–g), were screened for their antimicrobial activities and compared with three different references: vancomycin, ciprofloxacin, and fluconazole. They appeared to be good candidates as antibacterial agents against E. coli and S. aureus as well as antifungal agents against C. albicans. In general and for comparison, the antifungal activity of the final compounds 5(a–g) was more potent than their antibacterial activity. Finally, for the antimicrobial activity, the most active compound of these series was compound 5e, while compound 5g was the least active one.

Synthesis, Anticancer Activity, and Molecular Docking of New 1,2,3-Triazole Linked Tetrahydrocurcumin Derivatives.

Cancer is one of the deadliest diseases to humanity. There is significant progress in treating this disease, but developing some drugs that can fight this disease remains a challenge in the field of medical research. Thirteen new 1,2,3-triazole linked tetrahydrocurcumin derivatives were synthesized by click reaction, including a 1,3-dipolar cycloaddition reaction of tetrahydrocurcumin baring mono-alkyne with azides in good yields, and their in vitro anticancer activity against four cancer cell lines, including human cervical carcinoma (HeLa), human lung adenocarcinoma (A549), human hepatoma carcinoma (HepG2), and human colon carcinoma (HCT-116) were investigated using MTT(3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetraz-olium bromide) assay. The newly synthesized compounds had their structures identified using NMR HRMS and IR techniques. Some of prepared compounds, including compounds 4g and 4k, showed potent cytotoxic activity against four cancer cell lines compared to the positive control of cisplatin and tetrahydrocurcumin. Compound 4g exhibited anticancer activity with a IC50 value of 1.09 ± 0.17 μM against human colon carcinoma HCT-116 and 45.16 ± 0.92 μM against A549 cell lines compared to the positive controls of tetrahydrocurcumin and cisplatin. Moreover, further biological examination in HCT-116 cells showed that compound 4g can arrest the cell cycle at the G1 phase. A docking study revealed that the potential mechanism by which 4g exerts its anti-colon cancer effect may be through inhabiting the binding of APC-Asef. Compound 4g can be used as a promising lead for further exploration of potential anticancer agents.

Discovery of Novel (+)-Nootkatone-Based Amine Derivatives as Potential Insecticide Candidates.

To discover novel natural product-based insecticides, a series of (+)-nootkatone-based amine derivatives 3a-t were prepared and evaluated for their insecticidal activities against Mythimna separata Walker, Myzus persicae Sulzer, and Plutella xylostella Linnaeus. Insecticidal assays showed that most of the title (+)-nootkatone derivatives exhibited stronger insecticidal activities against three insect pests than the precursor (+)-nootkatone after the introduction of amine groups on the parent (+)-nootkatone. Compounds 3a, 3d, 3h, 3m, 3n, 3p, and 3r displayed more promising growth inhibitory (GI) effect against M. separata than the commercially available botanical insecticide toosendanin. Compound 3o exhibited the most potent aphicidal activity with an LD50 value of 0.011 μg/larvae, which was 2.09-fold higher than the positive control rotenone. Additionally, compounds 3g and 3n showed more promising larvicidal activity against P. xylostella with LC50 values of 260 and 230 mg/L, respectively, superior to that of rotenone (460 mg/L). Moreover, derivatives 3g and 3n exhibited better control efficacy toward P. xylostella than rotenone under greenhouse conditions. Preliminary mechanistic studies revealed that derivative 3n could inhibit the activity of glutathione S-transferase (GST) in P. xylostella and thus exerted larvicidal activity, and molecular docking further demonstrated that 3n could interact well with some amino acid residues of GST. Finally, the toxicity assay suggested that derivatives 3g and 3n were relatively less toxic to nontarget organisms. These findings will provide insights into the development of (+)-nootkatone derivatives as green pesticides.

Novel synthesis of a new class of substituted S-glycosylisothiourea derivatives and their conversion to 5-amino-1,2,4-triazoles

The one-pot reaction of potassium cyanocarbamimidothiolates with acetylated bromo sugars produced a novel class of substituted glycosylisothiourea derivatives 5a–h that demonstrated their Z-configuration. Some of the later compounds 5a–d were treated with NH3 in methanol at 25 °C, to afford the unprotected thioglycoside functionalized compounds 6a–c with excellent yields. To characterize the structure of the newly synthesized compounds, various techniques, such as elemental analysis and spectral data (13C NMR, IR, and 1H NMR) were employed. Furthermore, the substituted S-glycosylisothioureas 5 and 6 were subjected to a reaction with hydrazine hydrate, resulting in the formation of corresponding 5-amino-1,2,4-triazole derivatives 7a–d. The antibacterial properties of all newly synthesized compounds were thoroughly assessed and evaluated. Among these compounds, the most potent antimicrobial agents were found to be compounds 5a, 5g, 6a, 6b, and 6c.

Immunomodulation and anticancer evaluation of quinazoline-based thalidomide analogs: Design, synthesis, docking, and dynamic simulation

A new series of thalidomide analogs were synthesized and evaluated against HepG-2, HCT-116, PC3, and MCF-7. With IC50 values ranging from 2.41 to 14.78 μM, compounds 4c, 5g, and 7 demonstrated substantial potencies against all examined cell lines in comparison to thalidomide (IC50 = 32.12 - 76.91 μM)). The most active compounds were further evaluated for their in vitro immunomodulatory activities via IL6, TNF-α and human caspase-3 in MCF-7 cells using thalidomide as a positive control. Compounds 5g and 4c showed significant reductions in IL6 (80.65 %) and TNF-α (76.14 %), compared to thalidomide (45.11 % and 41.39, respectively). Furthermore, compound 4c exhibited a significant elevation in caspase-3 level (409.33 pg/mL) compared to thalidomide (349.55 pg/mL). In addition, the most active compounds were examined for their COX-I, COX-II, VEGFR inhibitory activities. Compound 5g was the most active member against COX-I (0.80 μM), compound 4c was the most active member against COX-II (0.80 μM), and compound 4c was the most active member against VEGFR (253 nM). Furthermore, the flowcytometry analyses revealed that compound 4c can arrest the cell line at Pre-G1 phase and induce a significant apoptotic effect (75.75 %) compared to control cells (2.62 %) and thalidomide (65.34 %). Our derivatives were subjected to molecular modeling to assess their binding to Cereblon and also dynamic simulations.

Triazole-benzenesulfonamide hybrids: Synthesis, biological evaluation, and molecular docking study as non-toxic antimicrobial and antioxidant agents

We have synthesized a library of twenty novel heterocyclic compounds having benzenesulfonamide and triazole moieties in their skeleton. Synthesized target compounds were tested for their inhibition potential against the growth of seven bacterial and one fungal pathogens. Free radical scavenging activities were also determined for the synthesized series of compounds using DPPH method. Furthermore, cytotoxicity studies of the target compounds were performed against mouse fibroblast animal cell lines and plant seed germination cell lines. To identify the binding modes, molecular docking of the most active antibacterial compound 3e and the most active antifungal compound 3g was performed in the active sites of target enzymes. All the tested compounds were found to be good antibacterial (MIC values = 4.9 – 37.8 µM) and antifungal (MIC values = 5.4 – 37.8 µM) agents. Results of antioxidant study showed that all the tested compounds are moderate to excellent free radical scavengers (% RSA values = 75.45 – 95.34). Furthermore, all were found safe against both the tested cell lines during cytotoxicity studies.

Design, Synthesis and Bioactivities of Novel Pyridyl Containing Pyrazole Oxime Ether Derivatives.

In this research, with an aim to develop novel pyrazole oxime ether derivatives possessing potential biological activity, thirty-two pyrazole oxime ethers, including a substituted pyridine ring, have been synthesized and structurally identified through 1H NMR, 13C NMR, and HRMS. Bioassay data indicated that most of these compounds owned strong insecticidal properties against Mythimna separata, Tetranychus cinnabarinus, Plutella xylostella, and Aphis medicaginis at a dosage of 500 μg/mL, and some title compounds were active towards Nilaparvata lugens at 500 μg/mL. Furthermore, some of the designed compounds had potent insecticidal effects against M. separata, T. cinnabarinus, or A. medicaginis at 100 μg/mL, with the mortalities of compounds 8a, 8c, 8d, 8e, 8f, 8g, 8o, 8s, 8v, 8x, and 8z against A. medicaginis, in particular, all reaching 100%. Even when the dosage was lowered to 20 μg/mL, compound 8s also expressed 50% insecticidal activity against M. separata, and compounds 8a, 8e, 8f, 8o, 8v, and 8x displayed more than 60% inhibition rates against A. medicaginis. The current results provided a significant basis for the rational design of biologically active pyrazole oxime ethers in future.

Design, Synthesis, and Cytotoxic Assessment of New Haloperidol Analogues as Potential Anticancer Compounds Targeting Sigma Receptors.

Sigma receptors (SRs), including SR1 and SR2 subtypes, have attracted increasing interest in recent years due to their involvement in a wide range of activities, including the modulation of opioid analgesia, neuroprotection, and potential anticancer activity. In this context, haloperidol (HAL), a commonly used antipsychotic drug, also possesses SR activity and cytotoxic effects. Herein, we describe the identification of novel SR ligands, obtained by a chemical hybridization approach. There wereendowed with pan-affinity for both SR subtypes and evaluated their potential anticancer activity against SH-SY5Y and HUH-7 cancer cell lines. Through a chemical hybridization approach, we identified novel compounds (4d, 4e, 4g, and 4j) with dual affinity for SR1 and SR2 receptors. These compounds were subjected to cytotoxicity testing using a resazurin assay. The results revealed potent cytotoxic effects against both cancer cell lines, with IC50 values comparable to HAL. Interestingly, the cytotoxic potency of the novel compounds resembled that of the SR1 antagonist HAL rather than the SR2 agonist siramesine (SRM), indicating the potential role of SR1 antagonism in their mechanism of action. The further exploration of their structure-activity relationships and their evaluation in additional cancer cell lines will elucidate their therapeutic potential and may pave the way for the development of novel anticancer agents that target SRs.

Design, synthesis, biological evaluation, and in silico studies of novel pyridopyridine derivatives as anticancer candidates targeting FMS kinase

Design and synthesis of novel 4-carboxamidopyrido[3,2-b]pyridine derivatives as novel rigid analogues of sorafenib are reported herein. The target compounds showed potent antiproliferative activities against a panel of NCI-60 cancer cell lines as well as hepatocellular carcinoma cell line. Compounds 8g and 9f were among the most promising derivatives in terms of effectiveness and safety. Therefore, they were further examined to demonstrate their ability to induce apoptosis and alter cell cycle progression in hepatocellular carcinoma cells. The most potent compounds were tested against a panel of kinases that indicated their selectivity against FMS kinase. Compounds 8g and 8h showed the most potent activities against FMS kinase with IC50 values of 21.5 and 73.9 nM, respectively. The two compounds were also tested in NanoBRET assay to investigate their ability to inhibit FMS kinase in cells (IC50 = 563 nM (8g) and 1347 nM (8h) vs. IC50 = 1654 nM for sorafenib). Furthermore, compounds 8g and 8h possess potent inhibitory activities against macrophages when investigated in bone marrow-derived macrophages (BMDM) assay (IC50 = 56 nM and 167 nM, respectively, 164 nM for sorafenib). The safety and selectivity of these compounds were confirmed when tested against normal cell lines. Their safety profile was further confirmed using hERG assay. In silico studies were carried out to investigate their binding modes in the active site of FMS kinase, and to develop a QSAR model for these new motifs.

Enzymatic synthesis of pyridine heterocyclic compounds and their thermal stability

An efficient method was discovered for catalyzing the esterification under air using Novozym 435 to obtain pyridine esters. The following conditions were found to be optimal: 60 mg of Novozyme 435, 5.0 mL of n-hexane, a molar ratio of 2:1 for nicotinic acids (0.4 mmol) to alcohols (0.2 mmol), 0.25 g of molecular sieve 3A, a revolution speed of 150 rpm, a reaction temperature of 50 °C, and reaction time of 48 h. Under nine cycles of Novozym 435, the 80 % yield was consistently obtained. Optimum conditions were used to synthesize 23 pyridine esters, including five novel compounds. Among them, gas chromatography-mass spectrometry-olfactometry (GC-MS-O) showed phenethyl nicotinate (3g), (E)-hex-4-en-1-yl nicotinate (3m), and octyl nicotinate (3n) possessed strong aromas. Thermogravimetric analysis (TG) revealed that the compounds 3g, 3m and 3n exhibited stability at the specified temperature. This finding provides theoretical support for adding pyridine esters fragrance to high-temperature processed food.

Synthesis, Characterization, DFT mechanistic study, Antibacterial Activity, Molecular modeling, and ADMET properties of novel chromone-isoxazole hybrids

A series of novel hybrid heterocycles incorporating isoxazole rings have been successfully synthesized, characterized, and evaluated for their antibacterial responses. The synthesized compounds were obtained by a subsequent N-alkylation and 1,3-dipolar cycloaddition reactions, their structures were identified by spectroscopy techniques (1H NMR, 13C NMR and 2D HSQC), and confirmed by mass spectrometry (HRMS). The spectroscopic data also show that the 1,3-dipolar cycloaddition (1,3-DC) reactions proceed in a regiospecific manner to give only one cycloadduct. The observed regioselectivity and the mechanistic study of the 1,3-DC reaction were further highlighted and explained using Density Functional Theory (DFT) calculations with the B3LYP/6–31G(d,p) basis set and Electron Localization Function (ELF) analysis. Moreover, the antibacterial screening shows that some compounds exhibit good efficacy against the tested bacterial strains. In addition, molecular docking studies were carried out to highlight the modes of interaction between the most active molecule 5d and receptors of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus strains. The results show that the studied compound was effectively docked to the active sites of each responsible protein with high protein-binding energies in kcal/mol. Finally, the prediction of ADMET properties suggests that almost all the hybrid compounds have good pharmacokinetic profiles, with no observed signs of toxicity, except for compounds 5e, 5f and 5g.

Insight on Some Newly Synthesized Trisubstituted Imidazolinones as VEGFR-2 Inhibitors.

Two series of ten new 1,2,4-trisubstituted imidazolin-5-ones were synthesized and screened against MCF-7 breast cancer and A549 lung cancer cell lines to test their potential in vitro anticancer activity. The results revealed preferential activity of the tested compounds toward MCF-7 cell lines compared to A549 cell lines. The most promising ten compounds (3a, 3c, 3f, 3g, 3h, 3i, 3j, 6a, 6f, and 6i) were subjected to VEGFR-2 enzyme inhibitory activity testing to further explore their mechanism of action. The tested compounds showed remarkable enzyme inhibition in micromolar concentrations ranging from 0.07 to 0.36 μM, compared with Sorafenib and Sunitinib with IC50 values of 0.06 and 0.12 μM, respectively. The most promising candidate, 3j, was further evaluated for its cell cycle phases, apoptotic induction ability, as well as its antiproliferative activity and inhibitory potential for endothelial cell migration, analyzed by a cell scratch assay. Furthermore, in silico studies were also performed to identify and detect the stability of the binding poses.

Design, synthesis, and structure–activity relationship of 2-chloro-3-formylquinoline containing hybrids as powerful antibacterial agents

This work aims to evaluate the antimicrobial activity of some new quinoline derivatives linked to pyrazole derivatives. The target compounds pyrazolylvinylquinoline 11a-g and 12a-g were achieved by the reaction of 2-chloro-6-nitro-3-quinolinecarboxaldehyde (4) with bromotriphenylphosphonylmethylpyrazole derivatives 9a,b to give the new quinoline derivatives 10a,b which in turn reacted with different aryl amines to afford 11a-g and 12a-g. Pyrazole derivatives 9a,b were obtained by the reaction of hydroxymethylpyrazole derivatives 8a,b with triphenylphosphine hydrobromide. Antimicrobial evaluation of the newly synthesized compounds showed that most of the new compounds appeared active toward Gram-positive bacteria more than Gram-negative bacteria. The biological evaluation of compounds 12d-g displayed the highest antimicrobial activity against the tested microorganism strains. Additionally, compounds 12d and 12f showed excellent activity against P. aeruginosa (MIC50 0.019 mg/mL), while compounds 11d, 11f, 12e, and 12g displayed good activity against the same microorganism (MIC50 0.07 mg/mL). On the other hand, most of the new compounds have moderate activity against E. coli. Compounds 12d and 12f showed excellent activity versus C. albicans in vitro antifungal activity (MIC50 0.15 mg/mL) comparing to or slightly lower than that of Fluconazole. Using molecular docking simulations, we evaluated the binding affinities and interactions of four chosen derivatives 12d-g with a target PDB code 3WT0 protein.

Exploration of morpholine-thiophene hybrid thiosemicarbazones for the treatment of ureolytic bacterial infections via targeting urease enzyme: Synthesis, biochemical screening and computational analysis

An important component of the pathogenicity of potentially pathogenic bacteria in humans is the urease enzyme. In order to avoid the detrimental impact of ureolytic bacterial infections, the inhibition of urease enzyme appears to be an appealing approach. Therefore, in the current study, morpholine-thiophene hybrid thiosemicarbazone derivatives (5a-i) were designed, synthesized and characterized through FTIR, 1H NMR, 13C NMR spectroscopy and mass spectrometry. A range of substituents including electron-rich, electron-deficient and inductively electron-withdrawing groups on the thiophene ring was successfully tolerated. The synthesized derivatives were evaluated in vitro for their potential to inhibit urease enzyme using the indophenol method. The majority of compounds were noticeably more potent than the conventional inhibitor, thiourea. The lead inhibitor, 2-(1-(5-chlorothiophen-2-yl)ethylidene)-N-(2-morpholinoethyl)hydrazinecarbothioamide (5g) inhibited the urease in an uncompetitive manner with an IC50 value of 3.80 ± 1.9 µM. The findings of the docking studies demonstrated that compound 5g has a strong affinity for the urease active site. Significant docking scores and efficient binding free energies were displayed by the lead inhibitor. Finally, the ADME properties of lead inhibitor (5g) suggested the druglikeness behavior with zero violation.

Investigating the antibacterial potential of novel N-Boc isatin Schiff bases: Combining synthesis with in-vitro and in-silico studies

The abstract explores into the antibacterial efficacy of newly synthesized N-Boc isatin Schiff bases against a range of pathogenic bacteria, including multidrug-resistant strains. The characterization of the synthesized compounds was achieved through various spectroscopic methods including 1H NMR, 13C NMR, and HRMS techniques, providing detailed structural insights. The in vitro antibacterial assessments were conducted via the agar diffusion method, revealing that compounds 3a, 3d, 3g, and 3j exhibited potent activity against both gram-positive (B. subtilis, MRSA) and gram-negative (E. coli) bacterial strains, providing objective data on their effectiveness. Furthermore, compound 3j, which featured bromine substitution at C5 of N-allyl isatin, displayed significant inhibition zones of 27 mm and 20 mm against E. coli and VRE, respectively, surpassing the activity of ciprofloxacin used as a standard drug molecule, thereby providing specific results. The molecular docking studies against E. coli Peptide Deformylase complex further confirmed the antibacterial potential of the synthesized compounds, adding a scientific basis for their efficacy. Additionally, in silico ADME predictions indicated favourable oral bioavailability, highlighting the promise of N-Boc substituted isatin Schiff bases as potential candidates for the development of novel antibacterial agents, thus contributing to the objective evaluation of their pharmacokinetic properties. Consequently, our studies demonstrated that these compounds not only possess significant antibacterial activity but also show promising pharmacokinetic properties, positioning them as strong candidates for the development of new antibacterial agents.

Novel Pyrido[4,3-d]pyrimidine Derivatives as Potential Sterol 14α-Demethylase Inhibitors: Design, Synthesis, Inhibitory Activity, and Molecular Modeling.

Thirty-four new pyrido[4,3-d]pyrimidine analogs were designed, synthesized, and characterized. The crystal structures for compounds 2c and 4f were measured by means of X-ray diffraction of single crystals. The bioassay results showed that most target compounds exhibited good fungicidal activities against Pyricularia oryzae, Rhizoctonia cerealis, Sclerotinia sclerotiorum, Botrytis cinerea, and Penicillium italicum at 16 μg/mL. Compounds 2l, 2m, 4f, and 4g possessed better fungicidal activities than the commercial fungicide epoxiconazole against B. cinerea. Their half maximal effective concentration (EC50) values were 0.191, 0.487, 0.369, 0.586, and 0.670 μg/mL, respectively. Furthermore, the inhibitory activities of the bioactive compounds were determined against sterol 14α-demethylase (CYP51). The results displayed that they had prominent activities. Compounds 2l, 2m, 4f, and 4g also showed better inhibitory activities than epoxiconazole against CYP51. Their half maximal inhibitory concentration (IC50) values were 0.219, 0.602, 0.422, 0.726, and 0.802 μg/mL, respectively. The results of molecular dynamics (MD) simulations exhibited that compounds 2l and 4f possessed a stronger affinity to CYP51 than epoxiconazole.

Design, synthesis and molecular docking study of novel triazole–quinazolinone hybrids as antimalarial and antitubercular agents

In a quest to discover new antimalarial and antitubercular drugs, we have designed and synthesized a series of novel triazole–quinazolinone hybrids. The in vitro screening of the triazole–quinazolinone hybrid entities against the plasmodium species P. falciparum offered potent antimalarial molecules 6c, 6d, 6f, 6g, 6j &6k owing comparable activity to the reference drugs. Furthermore, the target compounds were evaluated in vitro against Mycobacterium tuberculosis (MTB) H37Rv strain. Among the screened compounds, 6c, 6d and 6l were found to be the most active molecules with a MIC values of 19.57–40.68 μM. The cytotoxicity of the most active compounds was studied against RAW 264.7 cell line by MTT assay and no toxicity was observed. The computational study including drug likeness and ADMET profiling, DFT, and molecular docking study was done to explore the features of target molecules. The compounds 6a, 6g, and 6k exhibited highest binding affinity of −10.3 kcal/mol with docked molecular targets from M. tuberculosis. Molecular docking study indicates that all the molecules are binding to the falcipain 2 protease (PDB: 6SSZ) of the P. falciparum. Our findings indicated that these new triazole–quinazolinone hybrids may be considered hit molecules for further optimization studies.

Indole-based thiosemicarbazones for neurodegenerative diseases as prolyl oligopeptidase inhibitors

One of the highly expressed enzymes in the brain, prolyl specific oligopeptidase (POP), is a key target for the treatment of illnesses of the central nervous system including, autism spectrum, schizophrenia, Parkinson's, dementia, and Alzheimer's. In the current studies we report a series of indole based thiosemicarbazone as prolyl oligopeptidase (POP) inhibitors. Numerous approaches, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and mass-spectrometry (MS) procedures, were used to confirm the structures of all substances. These compounds were evaluated against POP interestingly all these tested molecules significantly inhibit POP in vitro at very low doses (5.74–25.30 µM). Compound 3g displayed the highest inhibition with IC50 value 5.74 ± 0.27 µM. Kinetic studies of compounds, 3g, revealed concentration dependent type of inhibition with Ki value 4.31 ± 0.0012 µM. Furthermore, molecular docking was also performed to understand the binding modes of compounds, which correlates with our in vitro outcomes.

Synthesis, Biological and Molecular Docking Studies of Thiazole-Thiadiazole derivatives as potential Anti-Tuberculosis Agents.

Tuberculosis remains a global health threat, with increasing infection rates and mortality despite existing anti-TB drugs. The present work focuses on the research findings regarding the development and evaluation of thiadiazole-linked thiazole derivatives as potential anti-tuberculosis agents. We present the synthesis data and confirm the compound structures using spectroscopic techniques. The current study reports twelve thiazole-thiadiazole compounds (5 a-5 l) for their anti-tuberculosis and related bioactivities. This paper emphasizes compounds 5 g, 5 i, and 5 l, which exhibited promising MIC values, leading to further in silico and interaction analysis. Pharmacophore mapping data included in the present analysis identified tubercular ThyX as potential drug targets. The compounds were evaluated for anti-tubercular activity using standard methods, revealing significant MIC values, particularly compound 5 l, with the best MIC value of 7.1285 μg/ml. Compounds 5 g and 5 i also demonstrated moderate to good MIC values against M. tuberculosis (H37Ra). Structural inspection of the docked poses revealed interactions such as hydrogen bonds, halogen bonds, and interactions containing Pi electron cloud, shedding light on conserved interactions with residues like Arg 95, Cys 43, His 69, and Arg 87 from the tubercular ThyX enzyme.

Antibiofilm effect of rubrolide analogues and derived lactams on single-species biofilms

In this study, a series of 26 lactones and lactams have been investigated for their effect against 14 single-species biofilm of oral commensal and pathogenic species (Streptococcus oralis, S. mitis, S. sanguinis, S. gordonii, Actinomyces naeslundii, A. viscosus, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Streptococcus mutans, S. sobrinus, S. salivarius, Veillonella parvula). At the dose of 128 mg/mL, all substances inhibited biofilm formation of S. oralis by more than 60 %, and 19 caused >60 % reduction in the biofilm production by S. sanguinis and A. naeslundi. In addition, 16 compounds showed better results against P. intermedia and F. nucleatum, inhibiting biofilm formation by > 50 %, while 8 compounds caused >40 % reduction in the biofilm formation of A. actinomycetemcomitans. Compounds 5b, 5c, 5d, 5f, and 7 g were the only ones active against S. mutans, and 6d was the only one active against S. sobrinus biofilm formation. Amongst all compounds tested, 24 maintained cell viability above 50 % after 24 h of exposure. In summary, a set of lactones and lactams capable of inhibiting single-species biofilms of oral commensal and pathogenic bacteria without showing significant cytotoxicity against oral epithelial cells were identified. These results highlight the potential of using such antibiofilm compounds as an alternative approach to control oral biofilms.