Good Antimycobacterial Activity Research Articles

Synthesis, Characterization, 'ADMET-SAR' Prediction, DPPH Assay, and Anti-Mycobacterium Study of 4-[(substituted benzyl) amino]benzo hydrazides and its Hydrazones as the Acyl-CoA Carboxylase, AccD5 Inhibitors.

Hydrazide-hydrazone derivatives have shown diverse biological activities, such as antitubercular (anti-TB), antibacterial, antifungal, anticancer, anti-inflammatory, antiviral, and antiprotozoal actions. Hydrazide-hydrazones contain azomethine (-NH-N=CH-) group connected with carbonyl group and are believed to be responsible for various pharmaceutical applications. They aid in the synthesis of different five-membered heterocyclic systems, such as oxadiazole, triazoles, etc. Methods: In the present study, various hydrazines/hydrazones were synthesized starting from 4- amino benzoic acid derivatives. Structures of all 9 newly synthesized compounds (6a-6d and 8a- 8e) were further characterized by using various spectroscopic methods, such as 1H-NMR (Nuclear Magnetic Resonance), FT-IR (Fourier-transform infrared spectroscopy), Gas chromatographymass spectrometry (GC-MS), etc. Furthermore, molecular docking analysis against the acyl-CoA carboxylase, AccD5 (PDB ID: 2A7S), was also carried out using the Glide module, which depicted good binding scores than standard drugs. The anti-tuberculosis activity of all the hydrazides and hydrazones (6a-6d and 8a-8e) were evaluated against the Mycobacterium tuberculosis H37 RV strain using the Alamar-Blue susceptibility (MABA) test. The activity was expressed as the minimum inhibitory concentration (MIC) in μg/mL values. The antioxidant activity was also carried out using a DPPH assay. Our findings demonstrated highly encouraging in-vitro results (MABA assay, MIC: 1.2 μg/mL) of hydrazones as depicted by good antimycobacterial activity. The antioxidant results showed a moderate to a good percentage of DPPH inhibition. Our in-silico ADMET analysis further suggested good pharmacokinetic and toxicity-free profiles of synthesized analogues (6a-6d and 8a-8e). Our results signify hydrazones/hydrazines as potential hit candidates against the future developments of potent and safer anti-TB agents.

One pot synthesis of 1,3,4-oxadiazoles by Lewis acid catalyst and their study of 2D-QSAR, antimicrobial and anti-tubercular activities

In the present work, Lewis acid catalyzed reactions have been carried out between mefenamic acid, substituted aldehyde and semicarbazide in the presence of ZnCl2 to give the final compounds (E)-N-(2-(5-((substitutedene)amino)-1,3,4-oxadiazol-2-yl)phenyl)-2,3-dimethylaniline, A. The synthesized compounds have been characterized by IR, 1H NMR, 13C NMR, mass spectral studies and biologically screened for the antimicrobial, antitubercular and antimalarial activities. Among the screened molecules, the molecules A1, A3, A4, A6, A8, A9, A10 show activity against different antibacterial species. The compounds, active against different antifugal species are A3, A7, A8, A9 against C. albicans, compound A3 is active against A. niger. Whereas, compound A9 shows good antimycobacterial activity. Compound A6 having 4-hydroxybenzenesubstituent exhibits promising activity against P. falciparum antimalerial parasite.

A Chitosan Hydrochloride Mediated, Simple and Efficient Approach for the Synthesis of Hydrazones, their in vitro Antimycobacterial Evaluations, and Molecular Modeling Studies (Part III)

AbstractA simple, eco-friendly and straightforward synthesis of hydrazones has been devised that is conducted in the presence of chitosan Hydrochloride (chitosan·HCl) as catalyst in aqueous-ethanol medium at room temperature. The current protocol offers metal-free synthesis, adaptability to large-scaleup, good yields, and quicker reaction time. All ten synthesized hydrazones also showed good antimycobacterial activity, with minimum inhibitory concentrations (MICs) ranging from 3.12 to 6.25 μg/mL. One of the products presented strong binding affinity against M. tuberculosis pantothenate synthetase (pdb id: 3IVX) with a Glide docking score of –8.803 kcal/mol. Molecular dynamics simulation analysis of its complex with 3IVX retained good stability over the simulation period of 20 ns.

Anti-Mycobacterial N-(2-Arylethyl)quinolin-3-amines Inspired by Marine Sponge-Derived Alkaloid.

The synthesis and evaluation of simplified analogs of marine sponge-derived alkaloid 3-(phenethylamino)demethyl(oxy)aaptamine were performed to develop novel anti-mycobacterial substances. Ring truncation of the tricyclic benzo[de][1,6]-naphthyridine skeleton effectively weakened the cytotoxicity of the natural product, and the resulting AC-ring analog exhibited good anti-mycobacterial activity. A structure-activity relationship (SAR) study, synthesizing and evaluating some analogs, demonstrated the specificity and importance of the N-(2-arylethyl)quinolin-3-amine skeleton as a promising scaffold for anti-mycobacterial lead compounds.

Design, synthesis and biological evaluation of alkynyl-containing maleimide derivatives for the treatment of drug-resistant tuberculosis

A series of alkynyl-containing maleimides with potent anti-tuberculosis (TB) activity was developed through a rigid group substitution strategy based on our previous study. Systematic optimization of the two side chains flanking the maleimide core led to new compounds with potent activity against Mycobacterium tuberculosis (MIC < 1 μg/mL) and low cytotoxicity (IC50 > 64 μg/mL). Among them, compound 29 not only possessed good activity against extensively drug-resistant TB and favorable hepatocyte stability, but also displayed good intracellular antimycobacterial activity in macrophages. This study lays a good foundation for identifying new alkynyl-containing maleimides as promising leads for treating drug-resistant TB.

Evaluation of Antitubercular activity and Hepatoprotective activity of Aristolochia bracteolata – in vitro study

India, with increased burden of tuberculosis (TB) cases, mandates the search for alternative antimycobacterial drugs. Medicinal plants have the potential to act against the mycobacterium with less or no side effects like hepatotoxicity caused by the most anti-TB drugs. This study is aimed to investigate the antimycobacterial activity of various extracts of whole plant, Aristolochia bracteolata against Mycobacterium tuberculosis H37Rv and hepatoprotective activity against anti-TB drug induced hepatotoxicity in HepG2 cell line. Microplate Alamar Blue Assay (MABA) is used to determine the Minimum Inhibitory Concentration (MIC) of samples for antimycobacterial activity and 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay to determine the effect of extract and standard, silymarin on isoniazid (INH) induced toxicity in HepG2 cells, based on the cell viability. The whole plant was extracted using petroleum ether, ethyl acetate and ethanol based on the polarity of solvents in the Soxhlet extractor successively and their yield value is determined. Phytochemical screening revealed the presence of constituents like alkaloids, terpenoids, flavonoids, phenols, tannins, saponin, steroids, carbohydrates and proteins. The results of MIC on Mycobacterium showed that the petroleum ether extract possess good antimycobacterial activity at 25µg/ml. It also showed good hepatoprotective activity against INH induced toxicity on increasing concentrations. So, the plant has the potential to act as adjunct to TB chemotherapy.

Identification of thiophene-benzenesulfonamide derivatives for the treatment of multidrug-resistant tuberculosis

A series of thiophene-benzenesulfonamide derivatives was designed and synthesized by exploring the structure-activity relationship of lead compounds 2,3-disubstituted thiophenes 25a and 297F as antituberculosis agents, which displayed potent antimycobacterial activity against drug-susceptible and clinically isolated drug-resistant tuberculosis. In particular, compound 17b, which had improved activity (minimum inhibitory concentration of 0.023 μg/mL) compared with the lead compounds, displayed good intracellular antimycobacterial activity in macrophages with a reduction of 1.29 log10 CFU. A druggability evaluation indicated that compound 17b had favorable hepatocyte stability, low cytotoxicity, and low hERG channel inhibition. Moreover, compound 17b exhibited modest in vivo efficacy in an acute mouse model of tuberculosis. In addition, the molecular docking study elucidated the binding mode of compound 17b in the active site of DprE1. Therefore, compound 17b may be a promising antituberculosis lead for further research.

Oxazolyl-Pyrimidines As Antibacterial And Antitubercular Agents: Synthesis, Biological Evaluation, in-silico ADMET And Molecular Docking Study

In search of novel biologically potent compounds, some new oxazolyl pyrimidines (7a-g) have been prepared in the current investigation. All new compounds were characterized using various spectroanalytical techniques such as FT-IR, NMR (1H & 13C), X-Ray single crystal diffractometer, elemental analysis, and mass spectral analysis. Further, the structure of one of the chalcone derivative 6b has been studied by X-Ray single crystal diffractometer. All new hybrids (7a-f) were screened in vitro for their antitubercular activity against M. tuberculosis H37Rv. All the newly prepared molecules exhibited good anti-mycobacterial activity. Amongst all compounds, 7d, 7e and 7f demonstrated the highest potency (MIC = 3.12 µg/mL). In addition, all the new derivatives were also screened for their in vitro antibacterial activity against three selected bacterial strains. New compounds have been docked for the CYP121 enzyme with favorable binding interactions. Further, in silico ADMET prediction and drug-like properties were also evaluated signifying that compounds are encouraging candidates for the design and development of new anti-TB agents with enriched activity and enhanced safety profile.

Novel Isoxazolone Based Azo Dyes: Synthesis, Characterization, Computational, Solvatochromic UV-Vis Absorption and Biological Studies

• Novel isoxazolone based azo dyes were synthesised and spectroscopically characterized • Computational study- Frontier molecular orbitals, Mulliken population analysis, Global reactive parameters, Molecular electrostatic potential and Reduced density gradient analysis • Solvatochromic UV-Vis absorption study was carried out • Antimycobacterial and anti-inflammatory efficacy were studied In this research investigation, novel isoxazolone-thiazole based azo dyes ( Io1-Io4 ) were synthesized by a conventional azo coupling reaction at 0-5°C. The structure elucidation was precisely assessed using various spectroscopic techniques like FT-IR, NMR and HRMS. Through computational study, molecular geometry, mulliken atomic charges and global reactive descriptors were investigated to get a better insight into the molecular properties. Molecular electrostatic potential (MEP) and reduced density gradient analysis (RDG) were also examined. The solvatochromic UV-Vis absorption study was performed using different solvents. A diffuse reflectance study was carried out to determine the optical band gap of the synthesized novel dyes ( Io1-Io4) . Biological efficacy towards antimycobacterial and anti-inflammatory activity was examined and the results revealed that, the compounds showed very good antimycobacterial and anti-inflammatory activity.

Identification of novel benzothiopyranones with ester and amide motifs derived from active metabolite as promising leads against Mycobacterium tuberculosis.

We reported three distinct series of novel benzothiopyranones, derived from an active metabolite (M-1) of anti-TB agent 6b. These small molecules were evaluated for their biological activities against a range of Mycobacterium tuberculosis (M.tuberculosis) strains. Preliminary druggability evaluation demonstrated that M-1 showed good aqueous solubility and hepatocyte stability. Benzothiopyranones with acyl, sulfonyl and phosphoryl groups exhibited potent invitro inhibitory activity against M.tuberculosis H37Rv and low cytotoxicity. In particular, compound 3d, containing a benzoate fragment, displayed marked metabolic stability and potent invitro activity against drug-resistant tuberculosis clinical strains. Further druggability evaluation based on the identified compounds 3d, 4e and 5b is ongoing for the discovery of promising anti-TB agents.

6-Fluorophenylbenzohydrazides inhibit Mycobacterium tuberculosis growth through alteration of tryptophan biosynthesis

A major constraint in reducing tuberculosis epidemic is the emergence of strains resistant to one or more of clinically approved antibiotics, which emphasizes the need of novel drugs with novel targets. Genetic knockout strains of Mycobacterium tuberculosis (Mtb) have established that tryptophan (Trp) biosynthesis is essential for the bacterium to survive in vivo and cause disease in animal models. An anthranilate-like compound, 6-FABA, was previously shown to synergize with the host immune response to Mtb infection in vivo. Herein, we present a class of anthranilate-like compounds endowed with good antimycobacterial activity and low cytotoxicity. We show how replacing the carboxylic moiety with a hydrazide led to a significant improvement in both activity and cytotoxicity relative to the parent compound 6-FABA. Several new benzohydrazides (compounds 20–31, 33, 34, 36, 38 and 39) showed good activities against Mtb (0.625 ≤ MIC≤6.25 μM) and demonstrated no detectable cytotoxicity against Vero cell assay (CC50 ≥ 1360 μM). The target preliminary studies confirmed the hypothesis that this new class of compounds inhibits Trp biosynthesis. Taken together, these findings indicate that fluorophenylbenzohydrazides represent good candidates to be assessed for drug discovery.

In vitro Activity of Selected Ethiopian Medicinal Plants against Mycobacterium bovis and Mycobacterium tuberculosis

Tuberculosis is a major global public health problem causing ill-health in millions of the world’s population. The emergence of drug resistant strains is a major challenge to the tuberculosis control programme. Hence, there is an urgent need for the development of new drugs. Herbs could be potential source of novel antituberculosis drugs due to their special attribute as a large source of therapeutic phytochemicals. The objective of this study was to investigate the in vitro antimycobacterial activity of the 80% methanol extracts of Erythrina brucei stem bark, Euphorbia candelabrum latex, Otostegia integrifolia leaf, Rumex abyssinicus root, and the chloroform extract of Vernonia amygdalina leaf on in vitro cultures of strains of Mycobactrium bovis and Mycobactrium tuberculosis. The extracts were obtained through cold maceration and soxhlet extraction, and essential oil was obtained by hydrodistillation. Macrodilution technique was used for determining the minimum inhibitory concentration (MIC) values. The MIC of the chloroform extract of V. amygdalina was 10 mg/ml against the mycobacterial strains tested. The 80% methanol extracts of E. brucei, O. integrifolia and R. abyssinicus were effective against M. bovis only with MIC ranging from 12.50 - 25.00 mg/ml. The oil from O. integrifolia was not active against the tested strains. E. candelabrum and oil from O. integrifolia failed to show antimycobacterial activity. In conclusion, the leaf extract of V. amygdalina is proven to be the most active plant that could be a potential source for antimycobacterial agents for human and bovine tuberculosis. Erythrina brucei, O. integrifolia and R. abyssinicus displayed good antimycobacterial activity against M. bovis suggesting their potential to be sources of new compounds for bovine tuberculosis.

Discovery of Novel Thiophene-arylamide Derivatives as DprE1 Inhibitors with Potent Antimycobacterial Activities.

In this study, we report the design and synthesis of a series of novel thiophene-arylamide compounds derived from the noncovalent decaprenylphosphoryl-β-d-ribose 2′-epimerase (DprE1) inhibitor TCA1 through a structure-based scaffold hopping strategy. Systematic optimization of the two side chains flanking the thiophene core led to new lead compounds bearing a thiophene-arylamide scaffold with potent antimycobacterial activity and low cytotoxicity. Compounds 23j, 24f, 25a, and 25b exhibited potent in vitro activity against both drug-susceptible (minimum inhibitory concentration (MIC) = 0.02–0.12 μg/mL) and drug-resistant (MIC = 0.031–0.24 μg/mL) tuberculosis strains while retaining potent DprE1 inhibition (half maximal inhibitory concentration (IC50) = 0.2–0.9 μg/mL) and good intracellular antimycobacterial activity. In addition, these compounds showed good hepatocyte stability and low inhibition of the human ether-à-go-go related gene (hERG) channel. The representative compound 25a with acceptable pharmacokinetic property demonstrated significant bactericidal activity in an acute mouse model of tuberculosis. Moreover, the molecular docking study of template compound 23j provides new insight into the discovery of novel antitubercular agents targeting DprE1.

Experience With Moxifloxacin for the Treatment of Latent Tuberculosis Infection in Liver Transplantation: A Single-Center Prospective Study.

Active tuberculosis (TB) after liver transplantation (LT) is associated with poor outcomes. Most cases arise from the reactivation of latent tuberculosis infection (LTBI). Current guidelines recommend LTBI treatment for all LT candidates with compensated cirrhosis, with isoniazid plus pyridoxine as the preferred regimen. Nevertheless, both completion rates and tolerability are low. Fluoroquinolones exhibit good antimycobacterial activity and favorable safety profile. We report our single-center experience with a 9-month moxifloxacin regimen (400 mg daily) for the treatment of LTBI in the LT setting. Between 2015 and 2019, 28 candidates and 10 recipients received moxifloxacin for a median of 260 days (interquartile range: 180 - 274). The 9-month course was completed in 60.5% (23/38) of patients. Adverse events (AEs) requiring permanent treatment discontinuation occurred in 21.0% (8/38) of patients (Clostridioides difficile infection [5 cases], diffuse arthralgias [2 cases], and hematologic toxicity [one case]). All AEs resolved without sequelae, with no episodes of moxifloxacin-associated liver toxicity. No cases of active TB were diagnosed following completion of therapy (cumulative follow-up of 19,475 patient-days). In conclusion, a 9-month moxifloxacin regimen appears to be a reasonable alternative to isoniazid for the treatment of LTBI among LT candidates and recipients, although a close follow-up is mandatory for an early recognition of associated AEs.

Synthesis, Characterization and Antimycobacterial Activity of Phenanthrenequinone Thiosemicarbazones and their Ruthenium and Zinc Complexes

The substituted phenanthrenequinone thiosemicarbazones (HL1, HL2 and HL3), and their metal complexes (M = Ru(II) or Zn(II); SM1, SM2, SM3 and SM4) were synthesized and characterized by FT-IR, 1H &amp; 13C NMR and ESI-MS. The spectral data IR, 1H &amp; 13C NMR and ESI-MS indicates two tridentate ligands coordinating in the form of an octahedral geometry. The gas phase geometry of all the zinc(II) and ruthenium(II) complexes was carried by using density functional theory (DFT). The antimycobacterial susceptibility testing at 100 μM of the complexes using resazurin microtiter plate assay resulted in growth inhibition. Complexes SM2, SM3 and SM4 showed good antimycobacterial activity at 100 μM concentration by using rifampicin as inhibition control.

Synthesis of New 3-Arylaminophthalides and 3-Indolyl-phthalides using Ammonium Chloride, Evaluation of their Anti-Mycobacterial Potential and Docking Study.

The study aims at the derivatization of "Phthalides" and synthesizes 3- arylaminophthalides & 3-indolyl-phthalides compounds, and evaluates their anti-tubercular and antioxidant activities. The study has also intended to employ the in silico methods for the identification of possible drug targets in Mycobacterium and evaluate the binding affinities of synthesized compounds. This report briefly explains the synthesis of phthalide derivatives using ammonium chloride. The synthesized compounds were characterized using spectral analysis. Resazurin Microtiter Assay (REMA) plate method was used to demonstrate the anti-mycobacterial activity of the synthesized compounds. An in-silico pharmacophore probing approach was used for target identification in Mycobacterium. The structural level interaction between the identified putative drug target and synthesized phthalides was studied using Lamarckian genetic algorithm-based software. In the present study, we report an effective, environmentally benign scheme for the synthesis of phthalide derivatives. Compounds 5c and 5d from the current series appear to possess good anti-mycobacterial activity. dCTP: deaminasedUTPase was identified as a putative drug target in Mycobacterium. The docking results clearly showed the interactive involvement of conserved residues of dCTP with the synthesized phthalide compounds. On the eve of evolving anti-TB drug resistance, the data on anti-tubercular and allied activities of the compounds in the present study demonstrates the enormous significance of these newly synthesized derivatives as possible candidate leads in the development of novel anti-tubercular agents. The docking results from the current report provide a structural rationale for the promising anti-tubercular activity demonstrated by 3-arylaminophthalides and 3-indolyl-phthalides compounds.

Anti-mycobacterial activity of two natural Bisanthraquinones: (+)-1,1′-Bislunatin and (+)-2,2′-Epicytoskyrin A

Tuberculosis is considered one of the leading death causes in the world by a single infectious agent, Mycobacterium tuberculosis (Mtb). The search for a new biologically active compound for the treatment of Tuberculosis is an urgent need due to the rise of multidrug-resistant phenomena. Endophytic fungi were known for a vast reservoir for bioactive secondary metabolites. Endophytic fungi, Diaporthe sp. GNBP-10 associated with gambier plant Uncaria gambier Roxb was able to produce two natural bisantharaquinone, (+)-1,1’-Bislunatin (Bis) and (+)-2,2’-Epicytoskyrin A (Epi), possessing strong antibacterial activities against the various pathogen. In this study, the biological activity screening of (Bis) and (Epi) will be extended by evaluating their activity against Mtb H37Rv. The in-vitro assay was conducted via determination of Minimum Inhibitory Concentration (MIC), nutrient-starvation Mtb, Biofilm Mtb formation, and Mtb-infected macrophage assay. Meanwhile, the in-silico screening was done by docking and Adsorption, Distribution, Metabolism, and Exertion (ADME) studies. Bis and Epi showed promising anti-tubercular activity, as shown by the MIC value of Bis, which is the same as rifampicin (standard drug) at 0.422 μM. Meanwhile, Epi carried out the same MIC value as isoniazid (standard drug) at 0.844 μM. Further investigation on in-vitro assay resulted in Epi and Bis, which were observed for having the ability to combat nutrient-starvation and biofilm of the Mtb model with relatively moderate activity in bacterial reduction with log reduction between 1-2 folds. The cytotoxicity study revealed that Bis possessed high toxicity at all tested concentrations, while the toxicity of Epi decreased as the tested concentrations decreased. Both compounds could reduce the number of Mtb infected into macrophages in 2 folds log reduction. The in-silico result via docking study shows that both compounds have good affinity with pantothenate kinase (PanK) enzyme with a glide score of -8.427 kcal/mol and -7.481 kcal/mol for Epi and Bis, respectively. This study suggests that Epi displayed a potency to be developed further as an anti-mycobacterial compound as it is shown by in-vitro assay, cytotoxicity, and in-silico study. Despite possessing good anti-mycobacterial activity, further studies such as QSAR (Quantitative-Structure Activity Relationship) is needed to improve the physicochemical properties of Epi while maintaining its biological properties.

Antimycobacterial Activity of Laurinterol and Aplysin from Laurencia johnstonii.

Marine environments represent a great opportunity for the discovery of compounds with a wide spectrum of bioactive properties. Due to their large variety and functions derived from natural selection, marine natural products may allow the identification of novel drugs based not only on newly discovered bioactive metabolites but also on already known compounds not yet thoroughly investigated. Since drug resistance has caused an increase in infections by Mycobacterium tuberculosis and nontuberculous mycobacteria, the re-evaluation of known bioactive metabolites has been suggested as a good approach to addressing this problem. In this sense, this study presents an evaluation of the in vitro effect of laurinterol and aplysin, two brominated sesquiterpenes isolated from Laurencia johnstonii, against nine M. tuberculosis strains and six nontuberculous mycobacteria (NTM). Laurinterol exhibited good antimycobacterial activity, especially against nontuberculous mycobacteria, being remarkable its effect against Mycobacterium abscessus, with minimum inhibitory concentration (MIC) values lower than those of the reference drug imipenem. This study provides further evidence for the antimycobacterial activity of some sesquiterpenes from L. johnstonii, which can be considered interesting lead compounds for the discovery of novel molecules to treat NTM infections.

Green synthesis of gold nanoparticles using extracellular metabolites of fish gut microbes and their antimicrobial properties.

In the present study, we synthesis nanoparticles using biosynthesis methods because of the eco-friendly approach. Gold nanoparticles were synthesized using extracellular metabolites of marine bacteria (Rastrelliger kanagurta, Selachimorpha sp., and Panna microdon). After the synthesis gold nanoparticles checked their antibacterial and antimycobacterial activities. Here we have few techniques that have been used for characterizing the gold nanoparticles followed by ultraviolet (UV)-visible spectrophotometer analysis, Fourier transform-infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscope (SEM), and transmission electron microscopy (TEM). We observed the formation of gold nanoparticles using UV-Vis spectroscopy (UV-Vis). FT-IR spectroscopy results of the extracellular metabolites showed that different characteristic functional groups are responsible for the bioreduction of gold ions. In the recent years, we used zebrafish for an animal model to estimate nanoparticle toxicity and biocompatibility. We tested toxicity of the gold nanoparticle using the zebrafish larvae that are growing exponentially. Sample 1 showed a good antimicrobial activity, and sample 5 showed a good antimycobacterial activity. Based on the UV spectrophotometer, sample 1 is used for further studies. Color change and UV spectrum confirmed gold nanoparticles. Based on the TEM and SEM particles, size was measured and ranged between 80 and 45nm, and most of the particles are spherical and are in rod shape. XRD result showed the gold nanoparticles with crystalline nature. Toxicity studies in the zebrafish larvae showed that 50μgml-1 showed less toxicity. Based on the studies, gold nanoparticle has good antibacterial and antimycobacterial activities. The present was concluded that gold nanoparticles have potential biocompatibility and less toxicity. Gold nanoparticles will be used as a drug molecule in pharmaceutical company and biomedicine application.

Identification of 2-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)amino)-N-phenylpropanamides as a novel class of potent DprE1 inhibitors

The identification of a novel series of DprE1 inhibitors based on a 2-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)amino)-N-phenylpropanamide scaffold is described herein. SAR exploration around the HTS hit 1 led to the identification of multiple analogues with potent DprE1 inhibition and good whole-cell antimycobacterial activity.