Search

The world now needs new antimicrobial drugs because many infections are resistant to existing treatments. Many microbial infections pose a significant global health challenge and a critical need for new, effective treatment. Soft corals are being explored for their potential as sources of new antimicrobial drugs. The present study aimed to determine the antimicrobial, antifungal, and antimycobacterial properties of the crude extract of coral Junceella delicata, collected from Madh island, Mumbai. The crude extract was prepared by adding an equal volume of methanol: dichloromethane (1:1) for 24 hours in the water bath at 45 °C. The sample was filtered through Whatman filter paper No. 1 and was subjected to concentrate in a rotary vacuum evaporator at 45° C. Further, antimycobacterial drugs viz. Isoniazid, Ethambutol, Pyrazinamide, Rifampicin, and Streptomycin were used to compare the activity with crude extract of the coral. It was observed that Coral J. delicata extract showed a zone of inhibition against all the bacterial strains viz., Klebsiella pneumonia (15 mm), Escherichia coli (15 mm), Salmonella typhi (14 mm), Pseudomonas aeruginosa (09 mm), Sarcina lutea (15 mm), Streptococcus pyogenes (12 mm), Corynebacterium diphtheria (27 mm), Staphylococcus aureus (28 mm), whereas antifungal activity was observed in Penicillium sp.(10 mm), Candida albicans (14 mm) and no activity was observed in Aspergillus sp. The Mycobacterium tuberculosis (MTB) strain showed sensitivity at (25µg/ml of coral extract, nearly close to the standard antituberculosis drug pyrazinamide (3.2µg/ml). The above results indicated that the crude extract of J. delicata had antibacterial activity nearly against the standard antituberculosis drug Pyrazinamide. The study suggests the crude extract of coral J. delicata can be used as an antimicrobial agent to cure different diseases, including tuberculosis. [ABSTRACT FROM AUTHOR]

Background: In recent years, ellagic acid has emerged as a focal point in pharmacological research, showcasing promising developments and potential therapeutic applications as a competitive inhibitor of Src homology phosphotyrosyl phosphatase 2 for the treatment of cancer, as a shielding impact that stimulates sirtuin 6 (SIRT 6), against nephrotoxicity induced by cisplatin, as adjuvant treatment in sickle cell anemia, as antiaging and to avoid mild cognitive impairment. Purpose: This review provides a concise overview of the latest advancements in ellagic acid research, highlighting novel pharmacological findings and emerging trends. Methodology: A comprehensive search of relevant literature was conducted to gather information on the pharmacological properties and therapeutic applications of ellagic acid. Studies investigating its antioxidant properties, anti-inflammatory effects, molecular interactions, and therapeutic implications were included in the analysis. Results: The review summarizes the multifaceted pharmacological landscape of ellagic acid, encompassing its antioxidant properties, anti-inflammatory effects, and potential therapeutic applications. It sheds light on its evolving role in modern medicine and underscores its significance as a promising avenue for future pharmaceutical exploration. Conclusion: The recent strides in ellagic acid development highlight its potential as a valuable therapeutic agent in various health conditions. Further research into its molecular interactions and clinical applications is warranted to fully harness its therapeutic potential and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Piper aduncum L. is widely distributed in tropical regions and the ethnobotanical uses of this species encompass medicinal applications for the treatment of respiratory, antimicrobial, and gynecological diseases. Chemical studies reveal a diverse array of secondary metabolites, including terpenes, flavonoids, and prenylated compounds. Extracts from P. aduncum have shown antibacterial, antifungal, and larvicidal activities. Our study explores the activity of extracts and partitions against Mycobacterium tuberculosis H37Rv, as well as the chemical diversity of the bioactive partition. This marks the first investigation of the bioactive partition of P. aduncum from agroecological cultivation. The ethyl acetate partition from the ethanolic leaf extract (PAEPL) was found to be the most active. PAEPL was subjected to column chromatography using Sephadex LH-20 and the obtained fractions were analyzed using UHPLC-HRMS/MS. The MS/MS data from the fractions were submitted to the online GNPS platform for the generation of the molecular network, which displayed 1714 nodes and 167 clusters. Compounds were identified via manual inspection and different libraries, allowing the annotation of 83 compounds, including flavonoids, benzoic acid derivatives, glycosides, free fatty acids, and glycerol-esterified fatty acids. This study provides the first chemical fingerprint of an antimycobacterial sample from P. aduncum cultivated in an agroecological system. [ABSTRACT FROM AUTHOR]

Nontuberculous mycobacteria (NTM) can cause a variety of infections, including serious pulmonary disease. Treatment encompasses polypharmacy, with a targeted regimen of 2–5 active medications, depending on site of infection, species, and clinical characteristics. Medications may include oral, intravenous, and inhalational routes. Medication acquisition can be challenging for numerous reasons, including investigational status, limited distribution models, and insurance prior authorization. Additionally, monitoring and managing adverse reactions and drug interactions is a unique skill set. While NTM is primarily medically managed, clinicians may not be familiar with the intricacies of medication selection, procurement, and monitoring. This review offers insights into the pharmacotherapeutic considerations of this highly complex disease state, including regimen design, medication acquisition, safety monitoring, relevant drug–drug interactions, and adverse drug reactions. [ABSTRACT FROM AUTHOR]

Many heterocyclic triazole rings and compounds containing triazole rings exhibit diverse biological activities. Heterocyclic derivatives of this class possess significant value for the discovery and development of new anticonvulsant medications as a result of successful synthesis of various triazole derivatives that hit the market for pharmaceuticals as CNS stimulants. The two isomers of triazole containing derivatives are 1,2,3-trizoles and 1,2,4-triazoles. From these two, 1, 2,4-triazole containing drugs exhibit a variety of pharmacological effects, including antimycobacterial, antitubercular, anticancer, anticonvulsant and herbicidal properties. Consequently, triazole-containing molecules function as potentially effective drug and may be useful for the design and development of new triazole derivatives that could be more efficacious and less toxic. This review summarizes data on various triazole derivatives and their significance. [ABSTRACT FROM AUTHOR]

Introduction: Recently, imidazooxazines have attracted more attention due to their therapeutic potential against tuberculosis (TB). The present study aimed to identify and develop potential inhibitors against Pks13-TE to combat the antimicrobial drug resistance of TB. Methods: Computer-aided drug design is a more highly valued technology than the traditional drug discovery approach. Herein, we computationally investigated a chemical dataset using QSAR models and virtually screened novel leads of imidazooxazines against the thioesterase domain, further subjecting them to molecular docking and dynamics simulation. Results: The present study identified two molecules, 1 and 3, promising leads with minimum energy conformations of −7.63 and −7.62 kcal, respectively, providing structural insight into Pks13 inhibition. The average values of MolSA, SASA, and PSA for molecules 1 and 3 were 382.41 Å, 77.65 Å, and 195.54 Å and 386.24 Å, 71.105 Å, and 184.46 Å, respectively. In conclusion, our research has demonstrated that imidazoxazines are promising leads to combat the resistance problem of TB. Among the two potent molecules 1 and 3, molecule 1 displayed favourable interactions in the active site with good stability, as confirmed by the RMSD, RMSF, RoG, H-bond, and SASA analyses. The Molecule 1 protein complex showed two strong hydrogen bonds, effectively maintained for 80–85 % of the simulation time, indicating its stability and potency. Conclusion: The identified two molecules and their conformations were highly stable; hence, these findings provide valuable insight into the evolution of new therapeutic agents to address the growing problem of TB and its resistance.

7-Methyljuglone (7-MJ) is a pure compound isolated from the roots of Euclea natalensis A. DC., a shrub indigenous to South Africa. It exhibits significant promise as a potential treatment for the highly communicable disease tuberculosis (TB), owing to its effective antimycobacterial activity against Mycobacterium tuberculosis. Despite its potential therapeutic benefits, 7-MJ has demonstrated in vitro cytotoxicity against various cancerous and non-cancerous cell lines, raising concerns about its safety for consumption by TB patients. Therefore, this review focuses on exploring the potential of poly-(lactide-co-glycolic) acid (PLGA) nanoparticles as a delivery system, which has been shown to decrease in vitro cytotoxicity, and 7-MJ as an effective antimycobacterial compound. [ABSTRACT FROM AUTHOR]

• Good safety profile and hepatoprotective effect is vital in tuberculosis chemotherapy. • Safety profile, hepatoprotective effect and selectivity index markers for herbal drug. • Plant extracts with LC 50 20 µg/mL and below are cytotoxic comparable with doxorubicin. • Menispermaceae species have global therapeutic effect due to their alkaloid content. Tuberculosis, caused by Mycobacterium tuberculosis , is a worldwide disease affecting millions of people. The rise of resistant strains, coupled with toxicity of current chemotherapy, requires effective alternatives against mycobacterial infections. Some plants from the Menispermaceae family have been used to treat tuberculosis and cough related symptoms. In this study, acetone, methanol:water (4:1), dichloromethane:methanol (1:1) and hot water extracts of different plant parts of Cissampelos owariensis, Cissampelos mucronata and Tinospora fragosa were tested against M. aurum, M. bovis, M. fortuitum, M. smegmatis and M. tuberculosis using a two-fold serial microdilution assay. Cytotoxicity of the active extracts was determined against Vero and HepG2 cells. The hepatoprotective effect of the active extracts was evaluated using rifampicin and acetaminophen as toxic drugs against HepG2 cells. The hot water leaf extracts were most active with promising minimum inhibitory concentration (MIC) values of 20 and 40 µg/mL against M. smegmatis and M. fortuitum respectively. The acetone extracts of C. owariensis, C. mucronata and T. fragosa had the lowest MIC values (0.03 – 1.67 mg/mL). The root extract of C. owariensis was not toxic to Vero cells while the leaf extract was more toxic. The acetone extract of C. mucronata leaves was toxic to Vero cells but the other extracts had low toxicity. The active leaf and root extracts had protective effects on rifampicin-induced toxicity on HepG2 cells. The root extract also had a protective effect on acetaminophen-induced toxicity on HepG2 cells but the leaf extract had no protective effect. The hot water extracts of C. owariensis, C. mucronata and T. fragosa had a more protective effect on the toxin-induced cells than the acetone extracts. These results support further investigation on the bioactive compounds in these plant extracts. [ABSTRACT FROM AUTHOR]

In the present study a series of ethyl 4-(substituted)-2-methyl-4H-benzo[4,5]thiazolo[3,2-a]pyrimidine-3-carboxylate and ethyl 4-(substituted)-8-methoxy-2-methyl-4H-benzo[4,5]thiazolo[3,2-a]pyrimidine-3-carboxylate have been synthesized and evaluated for their preliminary antibacterial, antifungal, antimycobacterial, antioxidant and antimalarial activity. Among all the synthesized derivatives some of the compounds exists good biological activity which is similar to that of standard drugs. These facts make the compounds interesting candidates for further evaluation of their efficacy in the treatment microbial, tubercular and malarial disease. [ABSTRACT FROM AUTHOR]

A series of levoglucosenone‐derived thiosemicarbazones have been designed and synthesized following a simple and straightforward procedure. The in vitro antimycobacterial activity of the full library were evaluated against M. tuberculosis H37Ra, with 4 compounds being active in the 1.9–10.7 μg/mL concentration range. To determine the influence of the thiosemicarbazone fragment, the synthetic precursors were analyzed, as well as 50 structurally diverse triazoles and isoxazoles derived from levoglucosenone. Comparing the observed activities with the levels of cell viability in L929 cells at the MIC, it can be concluded that the derivatives reported in this work represent interesting candidates for further development of promising antituberculosis agents. [ABSTRACT FROM AUTHOR]

A series of 5-(2-chloroquinolin-3-yl)-1,3,4-oxadiazole-2-amine (IIIa–IIIj) with different biological activities were designed and synthesized through the cyclization of semicarbazone. All the newly synthesized compounds were characterized by elemental analysis, 1H NMR, 13C NMR, FT-IR, and mass spectrometry. All the newly synthesized final compounds (IIIa–IIIj) were screened for in vitro antimicrobial activity by diffusion into agar wells using Gentamicin as the antibacterial agent and Fluconazole as the antifungal control. In addition, selected compounds were screened for antitubercular activity using Microplate Alamar Blue Assay (MABA). All the compounds were evaluated computationally for drug similarity using various pharmacokinetic studies and ADME-T characterization, then tested in vitro against Gram+ bacteria (Staphylococcus aureus and Bacillus subtilis), Gram– bacteria (S. typhi and P. aeruginosa), fungi (Aspergillus niger and Fusarium), as well as the Mycobacterium tuberculosis H37Rv strain, provided important information about activity against these strains. In the current study, we have discussed the method for the synthesis of 1,3,4-oxadiazole derivatives and summarized the role of compounds (IIIa), (IIIb), (IIId), (IIIg), (IIIh), and (IIIi) as potential antibacterial and antitubercular agents. We put forward further in vivo evaluation and biological activity evaluation for their use against these pathogens. [ABSTRACT FROM AUTHOR]

Objective: The aim of this research was the isolation, structure elucidation and evaluation of the bioactivity of natural products produced by an Aureobasidium pullulans fungal endophyte of the medicinal plant Thuja occidentalis. Methods: The natural products were isolated from an extract of A. pullulans culture broth by reversed-phase chromatography and their structures were elucidated based on analysis of HRESIMS and 1D/2D NMR data. The absolute configurations of the compounds were assigned by comparison of their electronic circular dichroism (ECD) and optical rotatory dispersion (ORD) data with values obtained for Boltzmann-weighted conformer ensembles calculated by density functional theory. Results/Conclusion: Two new C11-polyketides, aureobasidol A (1) and B (2), were isolated from the A. pullulans extract. Both polyketides showed selective but weak inhibitory activity against Mycobacterium tuberculosis in vitro. [ABSTRACT FROM AUTHOR]

Psoromic acid is a natural depsidone compound, often found in the lichen sources such as Usnea complanata and Rhizoplaca melanophthalma. It was reported to have versatile antioxidative, enzyme inhibitory and therapeutic properties. Studies on the biological activities of psoromic acid in the last decade have explored its potential in treating diseases like cancer, tuberculosis and cardiovascular disease. The present study extensively reviewed relevant works of literature from the sources like Scopus, Elsevier, MEDLINEPubMed, SpringerLink and Google Scholar. Biological activities such as antioxidant, gastroprotective effect, cardiovascular protection, anticancer, antitumor, antiviral response and enzyme inhibition were exclusively summarized. The proven therapeutic properties of psoromic acid suggested future clinical research in a larger sample size for the pharmacological acceptance of its antioxidant, antimicrobial and anticancer effects. The review may broaden the scope of knowledge of researchers to study pharmacokinetics, molecular mechanisms, efficacy and drug safety of psoromic acid and its derivatives. [ABSTRACT FROM AUTHOR]

Piper aduncum L. is widely distributed in tropical regions and the ethnobotanical uses of this species encompass medicinal applications for the treatment of respiratory, antimicrobial, and gynecological diseases. Chemical studies reveal a diverse array of secondary metabolites, including terpenes, flavonoids, and prenylated compounds. Extracts from P. aduncum have shown antibacterial, antifungal, and larvicidal activities. Our study explores the activity of extracts and partitions against Mycobacterium tuberculosis H37Rv, as well as the chemical diversity of the bioactive partition. This marks the first investigation of the bioactive partition of P. aduncum from agroecological cultivation. The ethyl acetate partition from the ethanolic leaf extract (PAEPL) was found to be the most active. PAEPL was subjected to column chromatography using Sephadex LH-20 and the obtained fractions were analyzed using UHPLC-HRMS/MS. The MS/MS data from the fractions were submitted to the online GNPS platform for the generation of the molecular network, which displayed 1714 nodes and 167 clusters. Compounds were identified via manual inspection and different libraries, allowing the annotation of 83 compounds, including flavonoids, benzoic acid derivatives, glycosides, free fatty acids, and glycerol-esterified fatty acids. This study provides the first chemical fingerprint of an antimycobacterial sample from P. aduncum cultivated in an agroecological system.

• Flavonoids from Chromolaena odorata exhibited antimycobacterial activity against pathogenic Mycobacterium bovis and M. tuberculosis H37RV. • Two flavonoids of Chromolaena odorata showed good hepatoprotective activity in HepG2 liver cells treated with rifampicin. • Flavonoids of Chromolaena odorata showed a relatively safe margin. • Chromolaena odorata compounds can serve as leads for the development of drugs against tuberculosis. Tuberculosis (TB) is currently rated as the 13th leading cause of mortality and the second leading cause of death after COVID-19, and above AIDS. Existing challenges relating to the development of multidrug-resistant strains and dangerous side effects of currently used drugs add impetus to the search for additional TB treatments. Hence, interest has grown in the use of medicinal plants as a source of bioactive preparations with efficacy against TB-causing organisms, and also with the ability to ameliorate the negative effects of TB drugs. This study aimed to evaluate the antimycobacterial and hepatoprotective potentials of extracts and isolated flavonoid compounds from invasive Chromolaena odorata. Test organisms used were pathogenic Mycobacterium bovis and M. tuberculosis H37RV, and the fast-growing M. aurum, M. fortuitum and M. smegmatis. The selectivity index (SI) values of the test substances were determined through cytotoxicity assays to promote these extracts and compounds as leads for the development of effective and safe anti-tubercular drugs. The antimycobacterial activity was evaluated using a serial microdilution method, and the SI was calculated from the 50% lethal concentrations calculated from cytotoxicity tests. Hepatoprotective activity was determined using HepG2 liver cells treated with rifampicin as a toxin. The extracts and compounds had a range of antimycobacterial activity with minimum inhibitory concentration (MIC) values ranging from 0.031 to 2.5 mg/mL. Two flavonoid compounds, 5,7,4′-trimethoxy flavanone and 5‑hydroxy-3,7,4′-trimethoxyflavone showed promising antimycobacterial potential, and minimal toxicity was observed, as most SI values were higher than 1. The flavonoid compound 5,7,4′-trimethoxy flavanone had the highest SI (6.452), which was against M. tuberculosis H37RV. The HepG2 cells were reduced to 65% due to toxicity by rifampicin, however, the flavonoid compounds were able to improve cell viability to between 81 and 89% at different concentrations tested. Results obtained indicate that C. odorata may serve as a lead for the development of safe and effective antimycobacterial and hepatoprotective drugs. [ABSTRACT FROM AUTHOR]

A series of new (E)-7-hydroxy-8-(amino-methyl)-4-styryl-2H-chromen-2-one derivatives has been synthesized. The protocol involves the reaction of Knoevenagel condensation product of 7-hydroxy-4-methylcoumarin with secondary aliphatic amine and equimolar formaldehyde under Mannich conditions. In vitro antimycobacterial activity of the developed compounds has been assessed against Mycobacterium smegmatis, a surrogate of the causal organism of tuberculosis Mycobacterium tuberculosis, by broth dilution assay. Among the tested compounds, 7a-f shows MIC value against the concentration 1000μg/mL. [ABSTRACT FROM AUTHOR]

Fruits of Citrus sinensis L. Osbeck var. Valencia contain hesperidin as a major flavanone glycoside. Hesperidin (H) was isolated from the peels of Valencia orange and formulated as hexosomal nanodispersions (F1) adopting the hot emulsification method. The antimycobacterial activity(anti-TB) was evaluated through a microplate Alamar blue (MABA) assay where F1 showed significant activity with MIC = 0.19 µM. To unravel the potential mechanism of the anti-TB, a molecular docking study of H using the Mycobacterial Dihydrofolate reductase (Mtb. DHFR) enzyme was performed. Hesperidin exhibited significant interactions with Mtb. DHFR active site. Sulforhodamine B assay was applied to evaluate cytotoxic activity against the lung cancer cell line (A-549). F1 showed a cytotoxic effect at IC50= 33 µM. It also has potent antiviral activity against Human Coronavirus 229E with IC50= 258.8 μM utilising crystal violet assay. Peels of Valencia orange could be a source of bioactive metabolites to control significant diseases. [ABSTRACT FROM AUTHOR]

• UPLC-MS/MS method developed to quantify obliquumol concentration in P. obliquum acetone extracts. • Ptaeroxylinol had MIC values as low as 8 µg/mL and 16 µg/mL against C. albicans ATCC 10,231 and cryptococcus neoformans respectively. • Ptaeroxylinol had some antimycobacterial activity with MIC value of 62.5 µg/mL against both M. bovis BCG and M. fortuitum. • Ptaeroxylinol had low toxicity against both vero and human liver (C3A) cells with IC 50 = 85.7 and 126.51 µg/mL respectively. Quantification of compounds in plant extracts is rarely conducted to determine variation in concentrations of bioactive constituents. The aim of the study was to develop a method using ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) to identify and quantify obliquumol (12- O -acetylptaeroxylinol) in Ptaeroxylon obliquum leaves collected from different localities in South Africa. Additionally, biological activity of a semi-synthesized derivative, ptaeroxylinol was investigated. Column chromatography was used to isolate obliquumol from P. obliquum leaves, and thereafter it was saponified to ptaeroxylinol. Ultra-performance liquid chromatography coupled to quadrupole time of flight mass spectrometry (UPLC-qTof-MS) was carried out on the different P. obliquum extracts to quantify obliquumol. A serial microdilution method was used to determine the minimum inhibitory concentration (MIC) against non-pathogenic mycobacteria and fungi. The cytotoxicity was determined using Vero monkey kidney and human liver (C3A) cells. A method was developed to isolate large quantities of obliquumol (0.14%) from dried P. obliquum leaves. The different P. obliquum acetone extracts had variable obliquumol concentrations between 0.1–38.5 µg/mg. Ptaeroxylinol had an MIC as low as 8 µg/mL and 16 µg/mL against Candida albicans ATCC 10,231 and Cryptococcus neoformans, respectively. With an IC 50 of 85.7 μg/mL for Vero cells and 126.51 μg/mL for C3A cells, respectively, ptaeroxylinol had low cytotoxicity to the cells tested. A UPLC-MS/MS method was developed to quantify obliquumol content in the P. obliquum acetone extracts. Ptaeroxylinol had good activity against C. albicans (MIC = 8 µg/mL) and it appears that the cleavage of the acetoxy to alcohol group played a role in the antimicrobial activity. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) remains a major health problem worldwide, and the emergence of multi-resistant strains to first-line drugs has become the biggest obstacle to its treatment. On the other hand, the incidence of non-tuberculous mycobacteria (NTM) in humans has increased remarkably in recent years. The search for new and better treatments against mycobacterial infections is a constant at the global level. Hence, in this study, we propose to investigate the antimycobacterial effect of the extracts and major compounds of Hedeoma drummondii against clinical isolates of Mycobacterium tuberculosis and non-tuberculous mycobacteria: M. abscessus, M. fortuitum, M. intracellulare, and M. gordonae. To determine the antimycobacterial activity, a microdilution assay was used to establish the minimum inhibitory concentration (MIC) of the different strains of Mycobacterium. The methanolic extract presented the best activity against M. tuberculosis, inhibiting ten of the twelve strains analyzed at a concentration < 2500 µg/mL; meanwhile, the hexanic extract presented the best activity against non-tuberculous mycobacteria (NTM) by inhibiting eight of the ten strains studied at ≤625 µg/mL. Moreover, there is a strong positive correlation between the antimycobacterial activity of pulegone and the hexanic extract against non-tuberculous strains, so this compound could serve as a predictability marker against these types of microorganisms. [ABSTRACT FROM AUTHOR]

New treatment regimens against tuberculosis (TB), which is still a serious social problem, are urgently needed. Herein, the anti‐TB potential of methanolic extract of Saraca asoca (S. asoca) was evaluated against Mycobacterium tuberculosis (Mtb) H37Rv strain and ∼88 % inhibition was achieved. To explore the interaction of phytochemicals with the targets of mycobacteria, 13 phytochemicals of S. asoca were docked with 3 receptors of Mtb H37Rv viz VapC2, PPE41, and CarD. Among these phytochemicals, Epicatechol, Leucocynadin and Procynidin were found most effective against Mtb H37Rv VapC2 protein with docking energy of −9.92110, −9.77605 and −10.62900 kcal/mol, respectively. Isolariciresinol and Procynidin were effective against CarD (−8.18264 and −9.97703 kcal/mol, respectively) and PPE41 (docking energy −9.16713 and −11.59770 kcal/mol, respectively). ADMET properties suggested good bioavailability of the active compounds. Molecular dynamics simulation studies revealed that Epicatechol complex with VapC2 protein stabilized after 20 ns and can be further explored for its anti‐TB potential via cell‐based co‐culture assays and animal studies. [ABSTRACT FROM AUTHOR]

7-Methyljuglone (7-MJ) is a pure compound isolated from the roots of Euclea natalensis A. DC., a shrub indigenous to South Africa. It exhibits significant promise as a potential treatment for the highly communicable disease tuberculosis (TB), owing to its effective antimycobacterial activity against Mycobacterium tuberculosis. Despite its potential therapeutic benefits, 7-MJ has demonstrated in vitro cytotoxicity against various cancerous and non-cancerous cell lines, raising concerns about its safety for consumption by TB patients. Therefore, this review focuses on exploring the potential of poly-(lactide-co-glycolic) acid (PLGA) nanoparticles as a delivery system, which has been shown to decrease in vitro cytotoxicity, and 7-MJ as an effective antimycobacterial compound.

Tuberculosis remains a serious killer among infectious diseases due to its incidence, mortality, and occurrence of resistant mycobacterial strains. The challenge to discover new antimycobacterial agents forced us to prepare a series of N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)(hetero)aryl-2-carboxamides 1–19 via the acylation of 6-aminobenzo[c][1,2]oxaborol-1(3H)-ol with various activated (hetero)arylcarboxylic acids. These novel compounds have been tested in vitro against a panel of clinically important fungi and bacteria, including mycobacteria. Some of the compounds inhibited the growth of mycobacteria in the range of micromolar concentrations and retained this activity also against multidrug-resistant clinical isolates. Half the maximal inhibitory concentrations against the HepG2 cell line indicated an acceptable toxicological profile. No growth inhibition of other bacteria and fungi demonstrated selectivity of the compounds against mycobacteria. The structure–activity relationships have been derived and supported with a molecular docking study, which confirmed a selectivity toward the potential target leucyl-tRNA synthetase without an impact on the human enzyme. The presented compounds can become important materials in antimycobacterial research. [ABSTRACT FROM AUTHOR]

In this study, 10 essential oils (EOs), from nine plants (Cinnamomum camphora, Curcuma longa, Citrus aurantium, Morinda citrifolia, Petroselinum crispum, Plectranthus amboinicus, Pittosporum senacia, Syzygium coriaceum, and Syzygium samarangense) were assessed for their antimicrobial, antiaging and antiproliferative properties. While only S. coriaceum, P. amboinicus (MIC: 0.50 mg/mL) and M. citrifolia (MIC: 2 mg/mL) EOs showed activity against Cutibacterium acnes, all EOs except S. samarangense EO demonstrated activity against Mycobacterium smegmatis (MIC: 0.125–0.50 mg/mL). The EOs were either fungistatic or fungicidal against one or both tested Candida species with minimum inhibitory/fungicidal concentrations of 0.016–32 mg/mL. The EOs also inhibited one or both key enzymes involved in skin aging, elastase and collagenase (IC50: 89.22–459.2 µg/mL; 0.17–0.18 mg/mL, respectively). Turmerone, previously identified in the C. longa EO, showed the highest binding affinity with the enzymes (binding energy: −5.11 and −6.64 kcal/mol). Only C. aurantium leaf, C. longa, P. amboinicus, P. senacia, S. coriaceum, and S. samarangense EOs were cytotoxic to the human malignant melanoma cells, UCT-MEL1 (IC50: 88.91–277.25 µg/mL). All the EOs, except M. citrifolia EO, were also cytotoxic to the human keratinocytes non-tumorigenic cells, HaCat (IC50: 33.73–250.90 µg/mL). Altogether, some interesting therapeutic properties of the EOs of pharmacological/cosmeceutical interests were observed, which warrants further investigations. [ABSTRACT FROM AUTHOR]

A new series of N-substituted-5-phenyl-[1,2,4]triazolo[1,5-c]quinazolin-2-amine (XIa–o) were synthesized by the nucleophilic substitution reaction of 4-(2-(methylthio)-5-phenyl-[1,2,4]triazolo quinazoline (X) with different aryl amines. The starting material 2-(methylthio)-5-phenyl-[1,2,4]triazolo quinazoline (X) was synthesized from anthranilic acid. All synthesized compounds were screened for their antitubercular, anti-HIV and antibacterial activity against selective gram-positive and gram-negative bacteria by agar dilution method. Among the series, compound N-(4-nitrophenyl)-5-phenyl-[1,2,4]triazolo[1,5-c]-quinazolin-2-amine (IXi) and N-(4-chlorophenyl)-5-phenyl-[1,2,4]triazolo[1,5-c]-quinazolin-2-amine (IXk) showed the most potent activity against E. coli, P. aeruginosa and S. epidermidis with the MIC of 3 µg/mL. The compound (IXi) exhibited the antitubercular activity at 6.25 µg/mL and anti-HIV activity at 7.15 µg/mL, respectively, against HIV1 and HIV2. It can be offered the potential for further optimization and development to new antitubercular and anti-HIV agents. The results obtained from this study confirm that the synthesized and biologically evaluated triazolo quinazolines showed promising antimicrobial, antitubercular and anti-HIV activities. [ABSTRACT FROM AUTHOR]

To extend our screening for novel antimycobacterial molecules, we have designed, synthesized, and biologically evaluated a library of 14 new hydrazide derivatives containing 1,3,4-oxadiazole core. A variety of mycobacterial strains, including some drug-resistant strains, were tested for antimycobacterial activity. Among the compounds tested, five showed high antimycobacterial activity (MIC values of 8 μg/mL) against M. tuberculosis H37Ra attenuated strain, and two derivatives were effective (MIC of 4 µg/mL) against pyrazinamide-resistant strains. Furthermore, the novel compounds were tested against the fungal C. albicans strain, showing no antimycotic activity, and thus demonstrating a good selectivity profile. Notably, they also exhibited low cytotoxicity against human SH-SY5Y cells. The molecular modeling carried out suggested a plausible mechanism of action towards the active site of the InhA enzyme, which confirmed our hypothesis. In conclusion, the active compounds were predicted in silico for ADME properties, and all proved to be potentially orally absorbed in humans. [ABSTRACT FROM AUTHOR]

• Synthesis and spectroscopic characterization of six new thiourea derivatives. • Three new solid-state crystal structures of the thiourea derivatives are reported. • Two compounds with potent MIC 90 (11.2 and 28.2 μM) results against tuberculosis. • Screening against HeLa cells showed two toxic compounds IC 50 (12.00 and 8.45 μM). In this study, thiourea derivatives were prepared to identify potentially effective compounds against tuberculosis and cervical cancer. The newly synthesized compounds, namely N-(cyclohexyl(methyl)carbomothioyl) benzamide (TU1), N-(cyclohexyl(methyl)carbamothioyl)-2-methylbenzamide (TU2), N-(dicyclohexylcarbamothioyl) benzamide (TU3), N-(dicyclohexylcarbamothioyl)-4-nitrobenzamide (TU4), N-(diphenylcarbamothioyl) benzamide (TU5), and N-(diphenylcarbamothioyl)-4-nitrobenzamide (TU6), were obtained in high purity and yields. The compounds were successfully characterized by infrared spectroscopy (IR), ultraviolet-visible spectroscopy (UV-Vis), nuclear magnetic resonance (NMR), single crystal X-ray diffractometer (SCXRD), mass spectrometry (MS) and the melting points (mp). Crystal structure analyses of TU1, TU2 and TU6 were carried out which showed, that in the solid state, the molecules were linked together by intermolecular hydrogen bonds, specifically N H⋯S and C H⋯O interactions. In-vitro testing against M. tuberculosis (Mtb) revealed compounds TU1 and TU2 to be the most potent with MIC 90 values of 28.2 and 11.2 μM, respectively. However, compounds TU4, TU5 , and TU6 , with MIC 90 values of 80.3, 82.8 and 107.7 µM, respectively, exhibit mild antituberculosis activity, whereas TU3 with a MIC 90 value of 752.7 µM is considered inactive against the Mtb strain. None of the compounds demonstrated significant selectivity for bacterial cells versus human cells and thus further studies could be dedicated to creating derivatives of TU1 and TU2 that are more selective. In vitro biological screening against HeLa cells revealed two highly toxic compounds, TU2 and TU6, with respective IC 50 values of 12.00 ± 1.21 μM (SI = 1.06) and 8.45 ± 1.21 μM (SI = 0.08); and two moderately toxic compounds, TU4 (IC 50 = 27.75 ± 1.15 µM; SI = 0.35) and TU5 (IC 50 = 23.66 ± 1.24 µM; SI = 0.29). [Display omitted] [ABSTRACT FROM AUTHOR]

• Ferrocenyl-substituted cyclohexenone and indazole derivatives as effective antimycobacterial agents. • Displayed the capacity to effectively suppress the formation of biofilms and disrupt pre-formed biofilms. • Indazole derivative 3b showed potential interactions with the target enzyme as revealed by docking studies and validated by enzyme assay. • Demonstrated good ADMET properties, passed Lipinski's filters, and demonstrated good drug-like properties. • The potential of compound 3b as a potential lead molecule that could be further optimized to develop ferrocene incorporating indazole based antimycobacterial agents. In response to the escalating threat of mycobacterial infections, including extensively drug-resistant tuberculosis (XDR) and multidrug-resistant tuberculosis (MDR), we synthesized novel ferrocene incorporating cyclohexenone and indazole derivatives. The compounds were synthesized via multistep reaction approach starting from chalcone precursors and evaluated against Mycobacterium fortuitum. The MIC and MBC values were calculated by following CLSI guidelines, with a focus on their ability to inhibit bacterial growth and disrupt biofilm formation. All the test compounds showed potent in vitro antimycobacterial activity against M. fortuitum. The MIC values range from 3.907 µg/mL to 500 µg/mL, whereas the MBC values range from 15.625 µg/mL to >500 µg/mL. Among the synthesized compounds, compound 3b exhibited potent antimycobacterial activity compared with standard drug Amikacin used to treat multidrug-resistant tuberculosis. 3b demonstrated significant inhibition of bacterial growth and showed the capacity to effectively suppress biofilm formation and disrupt pre-existing biofilms. This molecule also displayed favourable ADMET profile and good oral bioavailability, besides showing potential interactions with the target enzyme as revealed by docking studies and validated by enzyme assay. Collectively, these studies position 3b as a potential lead molecule that could be further optimized to develop ferrocene incorporating indazole based antimycobacterial agents. [ABSTRACT FROM AUTHOR]

Background: Aphloia theiformis is used in Makete district, Tanzania, and other areas by HIV and AIDS patients as a weight loss remedy and for treatment of tuberculosis. However, there is no literature information on its antimycobacterial activity. Purpose: To evaluate antimycobacterial activity of A. theiformis root ethanolic extract and isolated compounds. Methods: The broth microdilution method was used to test the crude root ethanolic extract for activity against different non-pathogenic mycobacteria. Bioautography was used to identify the active constituents. Isolation of the active compounds was carried out using bioassay-guided fractionation. Chemical structures of compounds were established by comparison of their spectra with literature spectral data. The isolated compounds and some fractions were screened for activity against M. tuberculosis (MTB) subtype H37Rv and clinical isolates of MTB including strains resistant to rifampicin. Results: The 80% ethanolic extract of A. theiformis displayed activity against all non-pathogenic mycobacteria. The most active fraction was the ethyl acetate fraction from which two compounds were isolated; an epicatechin dimer; proanthocyanidin A2 (1) and tormentic acid (2) belonging to ursane pentacyclic triterpenoid. Compound (1) had MICs of 60.7 µM against Mycobacterium madagascariense and Mycobacterium indicus pranii and 255 µM against both standard MTB (H37Rv) and clinical isolate of rifampicin-resistant MTB. Conclusion: This study provides evidence in support of the use of A. theiformis extracts by traditional health practitioners for the management of tuberculosis. We recommend more studies to further assess efficacy and safety of the plant constituents using different models.

Multidrug-resistant tuberculosis (MDR-TB) poses a significant threat to mankind and as such earned its place on the WHO list of priority pathogens. New antimycobacterials with a mechanism of action different to currently used agents are highly required. This study presents the design, synthesis, and biological evaluation of 3-acylaminopyrazine-2-carboxamides derived from a previously reported inhibitor of human prolyl-tRNA synthetase. Compounds were evaluated in vitro against various strains of mycobacteria, pathogenic bacteria, and fungi of clinical significance. In general, high activity against mycobacteria was noted, while the antibacterial and antifungal activity was minimal. The most active compounds were 4'-substituted 3-(benzamido)pyrazine-2-carboxamides, exerting MIC (Minimum Inhibitory Concentration) from 1.95 to 31.25 µg/mL. Detailed structure–activity relationships were established and rationalized in silico with regard to mycobacterial ProRS as a probable target. The active compounds preserved their activity even against multidrug-resistant strains of Mycobacterium tuberculosis. At the same time, they were non-cytotoxic against HepG2 human hepatocellular carcinoma cells. This project is the first step in the successful repurposing of inhibitors of human ProRS to inhibitors of mycobacterial ProRS with antimycobacterial activity. [ABSTRACT FROM AUTHOR]

Background: The aim of the current study was to examine the potential of a rifampicin-loaded metal–organic framework (RIF@ZIF-8) for management of tuberculosis. Materials and Methods: RIF@ZIF-8 was developed using a simple, economic, and environmentally friendly ultrasonication method. Furthermore, the developed metal–organic framework (MOF) formulations were subjected to physicochemical characterization analyses such as Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffractometry, thermogravimetric analysis, field emission-scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), and UV spectroscopy. In addition, in vitro release, powder flow characterization, in vitro lung deposition, and efficacy studies against the Mycobacterium tuberculosis (MTB) H37Rv strain were performed. Results: Physicochemical characterization confirms its spherical shape and drug loading, whereas in vitro release analysis shows 80.5 ± 5.5% release of the drug from the loaded formulation within 48 hours. Furthermore, powder flow properties suggested that the nature of MOFs is free flowing. Additionally, in vitro lung deposition studies indicated an emission fraction of 88.02 ± 10.23% for the emitted dose and circa 21% fine particle fraction. The mass median aerodynamic diameter and geometric standard deviation were found to be 4.42 ± 0.07 μm and 1.55 ± 01 μm, respectively. The in vitro aerosol performance study demonstrated higher deposition at stages 3, 4, and 5 of the cascade impactors, which simulate deep lung delivery in terms of the trachea–primary bronchus and secondary and terminal bronchi of the human lung, respectively. Moreover, RIF@ZIF-8 exhibited improved antimycobacterial activity (0.0125 mg/mL) vis-à-vis an unformulated drug (0.025 mg/mL) against the MTB H37Rv strain, using the BACTEC 460TB system. Conclusions: Therefore, MOFs could be promising nanocarriers for targeting lungs and overcoming the hepatotoxicity associated with antituberculosis drugs requiring inhalation administration. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a massive problem for public health and is the leading cause of illness and death worldwide. Rosemary (Rosmarinus officinalis) is used traditionally to treat many diseases, such as infections of the lungs including pulmonary TB. R. officinalis was collected from Al Anbar Governorate, Iraq, and was extracted with deep eutectic solvents (DESs) of many different kinds and with conventional water solvent. The antimycobacterial activities of the R. officinalis extracts were tested against multidrug-resistant (MDR) Mycobacterium tuberculosis by agar disc diffusion assay. Minimum inhibitory concentrations were measured spectrophotometrically at 570 nm. Then, a time-kill assay and cell membrane integrity analysis were conducted to investigate the effects of the most active extracts on cell growth. The in vitro cytotoxicity of the most active extracts was evaluated against Rat Embryonic Fibroblasts (REF) cell line by MTT assay. Liquid chromatography-mass spectrometry (LC-MS) was conducted to analyze the chemical components of the most active extracts. At 200 mg/mL concentration, a significant inhibition activity was seen in DES2: Tailor (DIZ = 17.33 ± 1.15 mm), followed by DES3: ChGl, DES1: LGH and DES4: ChXl. The best result was DES2: Tailor, which had a MIC of 3.12 mg/mL and an MBC of 12.5 mg/mL. The DES2 extract exhibited a high drop in the number of colonies over time, killing more than 80 colonies. The main phytochemical compounds of the R. officinalis extract were camphene, camphenilol, α-pinene, limonene, apigenin, camphor, carnosol, linalool and myrcene. R. officinalis extracts obtained by DESs have shown evident power in treating tuberculosis, and extraction by DES is a greener procedure than the methods involving conventional extraction solvents. As a result, additional research into the application of DES should be considered. [ABSTRACT FROM AUTHOR]

Isoniazid (INH) is one of the key molecules employed in the treatment of tuberculosis (TB), the most deadly infectious disease worldwide. However, the efficacy of this cornerstone drug has seriously decreased due to emerging INH-resistant strains of Mycobacterium tuberculosis (Mtb). In the present study, we aimed to chemically tailor INH to overcome this resistance. We obtained thirteen novel compounds by linking INH to in-house synthesized sulfonate esters via a hydrazone bridge (SIH1–SIH13). Following structural characterization by FTIR, 1H NMR, 13C NMR, and HRMS, all compounds were screened for their antitubercular activity against Mtb H37Rv strain and INH-resistant clinical isolates carrying katG and inhA mutations. Additionally, the cytotoxic effects of SIH1–SIH13 were assessed on three different healthy host cell lines; HEK293, IMR-90, and BEAS-2B. Based on the obtained data, the synthesized compounds appeared as attractive antimycobacterial drug candidates with low cytotoxicity. Moreover, the stability of the hydrazone moiety in the chemical structure of the final compounds was confirmed by using UV/Vis spectroscopy in both aqueous medium and DMSO. Subsequently, the compounds were tested for their inhibitory activities against enoyl acyl carrier protein reductase (InhA), the primary target enzyme of INH. Although most of the synthesized compounds are hosted by the InhA binding pocket, SIH1–SIH13 do not primarily show their antitubercular activities by direct InhA inhibition. Finally, in silico determination of important physicochemical parameters of the molecules showed that SIH1–SIH13 adhered to Lipinski's rule of five. Overall, our study revealed a new strategy for modifying INH to cope with the emerging drug-resistant strains of Mtb. [ABSTRACT FROM AUTHOR]

Marine invertebrate sponges are a rich source of new bioactive substances. The objective of this investigation was to isolate the anti-mycobacterium bioactive compounds from sponge Haliclona sp. A new alkaloid (1) was obtained through bioassay-guided purification together with eight previously known substances, including cyclostellettamines A (5), B (6), C (7), E (8), and F (9) and the haliclocyclamines A (2), B (3), and C. The structures of 1-9 were established applying spectroscopic analysis, including 1D NMR (1H and 13C-NMR), 2D NMR (HMQC, HMBC, 1H-1H COSY), mass spectroscopy, IR, and UV. Furthermore, the findings revealed that the compounds exhibited inhibitory activity against Mycobacterium smegmatis at 10 µg/disc. [ABSTRACT FROM AUTHOR]

With tuberculosis, the emergence of fluoroquinolone resistance erodes the ability of treatment to interrupt the progression of MDR-TB to XDR-TB. One way to reduce the emergence of resistance is to identify heteroresistant infections in which subpopulations of resistant mutants are likely to expand and make the infections fully resistant: treatment modification can be instituted to suppress mutant enrichment. Rapid DNA-based detection methods exploit the finding that fluoroquinolone-resistant substitutions occur largely in a few codons of DNA gyrase. A second approach for restricting the emergence of resistance involves understanding fluoroquinolone lethality through studies of antimicrobial tolerance, a condition in which bacteria fail to be killed even though their growth is blocked by lethal agents. Studies with Escherichia coli guide work with Mycobacterium tuberculosis. Lethal action, which is mechanistically distinct from blocking growth, is associated with a surge in respiration and reactive oxygen species (ROS). Mutations in carbohydrate metabolism that attenuate ROS accumulation create pan-tolerance to antimicrobials, disinfectants, and environmental stressors. These observations indicate the existence of a general death pathway with respect to stressors. M. tuberculosis displays a variation on the death pathway idea, as stress-induced ROS is generated by NADH-mediated reductive stress rather than by respiration. A third approach, which emerges from lethality studies, uses a small molecule, N-acetyl cysteine, to artificially increase respiration and additional ROS accumulation. That enhances moxifloxacin lethality with M. tuberculosis in culture, during infection of cultured macrophages, and with infection of mice. Addition of ROS stimulators to fluoroquinolone treatment of tuberculosis constitutes a new direction for suppressing the transition of MDRTB to XDR-TB. [ABSTRACT FROM AUTHOR]

The recent emergence of drug‐resistant strains of Mycobacterium tuberculosis (Mtb) has complicated and significantly slowed efforts to eradicate and/or reduce the worldwide incidence of life‐threatening acute and chronic cases of tuberculosis. To overcome this setback, researchers have increased the intensity of their work to identify new small‐molecule compounds that are expected to remain efficacious antimicrobials against Mtb. Here, we describe our effort to apply the principles of molecular hybridization to synthesize 16 compounds carrying thiophene and thiazole rings beside the core urea functionality (TTU1–TTU16). Following extensive structural characterization, the obtained compounds were initially evaluated for their antimycobacterial activity against Mtb H37Rv. Subsequently, three derivatives standing out with their anti‐Mtb activity profiles and low cytotoxicity (TTU5, TTU6, and TTU12) were tested on isoniazid‐resistant clinical isolates carrying katG and inhA mutations. Additionally, due to their pharmacophore similarities to the well‐known InhA inhibitors, the molecules were screened for their enoyl acyl carrier protein reductase (InhA) inhibitory potentials. Molecular docking studies were performed to support the experimental enzyme inhibition data. Finally, drug‐likeness of the selected compounds was established by theoretical calculations of physicochemical descriptors. [ABSTRACT FROM AUTHOR]

In previous studies, we demonstrated the potent activity of a library of 25 N,N'-disubstituted diamines (NNDDA) toward Trypanosomatid and Apicomplexa parasites. Considering the structure similarity between this collection and SQ109, an antituberculosis compound, and its compelling antiparasitic properties, we aimed to repurpose this library for tuberculosis treatment. We assayed this collection against Mycobacterium tuberculosis H37Rv and M. avium, obtaining several compounds with MIC values below 10 µM. The most active analogs were also evaluated against M. smegmatis, a non-pathogenic species, and the non-tuberculosis mycobacteria M. abscessus, M. kansasii, and M. fortuitum. 3c stands out as the lead mycobacterial compound of the collection, with potent activity against M. tuberculosis (minimal inhibitory concentration [MIC] = 3.4 µM) and moderate activity against M. smegmatis, M. kansasii, and M. fortuitum (all with MIC values of 26.8 µM). To unravel the mechanism of action, we employed the web-based platform Polypharmacology Browser 2 (PPB2), obtaining carbonic anhydrases as potential drug targets. Nevertheless, none of the compounds displayed experimental inhibition. In summary, our study confirms the validity of the repurposing approach and underscores the antimycobacterial potential of NNDDA compounds, especially the analog 3c, setting a stepping stone for further studies., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

With tuberculosis, the emergence of fluoroquinolone resistance erodes the ability of treatment to interrupt the progression of MDR-TB to XDR-TB. One way to reduce the emergence of resistance is to identify heteroresistant infections in which subpopulations of resistant mutants are likely to expand and make the infections fully resistant: treatment modification can be instituted to suppress mutant enrichment. Rapid DNA-based detection methods exploit the finding that fluoroquinolone-resistant substitutions occur largely in a few codons of DNA gyrase. A second approach for restricting the emergence of resistance involves understanding fluoroquinolone lethality through studies of antimicrobial tolerance, a condition in which bacteria fail to be killed even though their growth is blocked by lethal agents. Studies with Escherichia coli guide work with Mycobacterium tuberculosis. Lethal action, which is mechanistically distinct from blocking growth, is associated with a surge in respiration and reactive oxygen species (ROS). Mutations in carbohydrate metabolism that attenuate ROS accumulation create pan-tolerance to antimicrobials, disinfectants, and environmental stressors. These observations indicate the existence of a general death pathway with respect to stressors. M. tuberculosis displays a variation on the death pathway idea, as stress-induced ROS is generated by NADH-mediated reductive stress rather than by respiration. A third approach, which emerges from lethality studies, uses a small molecule, N-acetyl cysteine, to artificially increase respiration and additional ROS accumulation. That enhances moxifloxacin lethality with M. tuberculosis in culture, during infection of cultured macrophages, and with infection of mice. Addition of ROS stimulators to fluoroquinolone treatment of tuberculosis constitutes a new direction for suppressing the transition of MDR-TB to XDR-TB.

Two Nigerian medicinal plants Cissampelos owariensis and Cissampelos mucronata (Menispermaceae) are commonly used in traditional medicine for the management of tuberculosis-related symptoms. The rationale behind this study is based on the fact that the two plants possess similar appearances thus often mistaken for each other, and both have also been reported for antimycobacterial activity. Hence, the objective of this study was to profile the chemical constituents of the two plants, establish their respective chromatographic fingerprints as an identity marker, and compare their bioactivities against two Mycobacterium species. Aqueous methanol extract of the roots of both plants was screened for their secondary metabolite contents and were also evaluated for their action against Bacillus Camille Guerin and Mycobacterium smegmatis. Alkaloids, flavonoids, steroids and terpenes were present in both plant extracts. In-vitro antimycobacterial assay showed that the extracts of C. owariensis and C. mucronata inhibited the growth of M. smegmatis at 3.13 mg/mL and 6.25 mg/mL, respectively and was bactericidal at 6.25 mg/mL and 12.5 mg/mL, respectively. Against BCG, the extract of C. owariensis displayed inhibitory and bactericidal properties at 0.39 mg/mL and 0.78 mg/mL, respectively, and C. mucronata at 3.13 mg/mL and 6.25 mg/mL, respectively. This indicates that both strains of the Mycobacterium were more susceptible to C. owariensis than C. mucronata invitro. The HPLC fingerprint results were non-identical for the two plant extracts, and comparison with their alkaloid fraction chromatograph revealed that the crude extracts consisted largely of alkaloids. This study has established distinguishable chromatographic profiles between the two species. [ABSTRACT FROM AUTHOR]

Herein we summarize the production of silver/copper oxide nanocomposites (Ag/CuO NCs) by a facile solution combustion method with the aid of abio-fuel as reductant. Powder XRD results revealed the formation of Ag/CuO NCs with average crystallite size ranging from 20 to 25 nm. These NCs were tested for their antimycobacterial activity against four mycobacterium species namely Mycobacterium tuberculosis H37Rv ATCC 27294, Mycobacterium abscessus ATCC 19977, Mycobacterium fortuitum ATCC 6841, Mycobacterium chelonae ATCC and anticarcinogenic activity on breast cancer cell line MDA-MB-231. Scavenging activity was evaluated by the 2, 2-diphenyl-1-picrylhydrazyl hydrate (DPPH) method. Results indicated that the Ag/CuO NCs had higher anticancer and slightly better scavenging activities than the undoped CuO nanoparticles. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis which has become prevalent due to the emergence of resistant M. tuberculosis strains. The use of essential oils (EOs) as potential anti-infective agents to treat microbial infections, including TB, offers promise due to their long historical use and low adverse effects. The current study aimed to investigate the in vitro anti-TB activity of 85 commercial EOs, and identify compounds responsible for the activity, using a biochemometrics approach. A microdilution assay was used to determine the antimycobacterial activity of the EOs towards some non-pathogenic Mycobacterium strains. In parallel, an Alamar blue assay was used to investigate antimycobacterial activity towards the pathogenic M. tuberculosis strain. Chemical profiling of the EOs was performed using gas chromatography-mass spectrometry (GC-MS) analysis. Biochemometrics filtered out putative biomarkers using orthogonal projections to latent structures discriminant analysis (OPLS-DA). In silico modeling was performed to identify potential therapeutic targets of the active biomarkers. Broad-spectrum antimycobacterial activity was observed for Cinnamomum zeylanicum (bark) (MICs = 1.00, 0.50, 0.25 and 0.008 mg/mL) and Levisticum officinale (MICs = 0.50, 0.5, 0.5 and 0.004 mg/mL) towards M. smegmatis, M. fortuitum, M. gordonae and M. tuberculosis, respectively. Biochemometrics predicted cinnamaldehyde, thymol and eugenol as putative biomarkers. Molecular docking demonstrated that cinnamaldehyde could serve as a scaffold for developing a novel class of antimicrobial compounds by targeting FtsZ and PknB from M. tuberculosis. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is an infectious disease caused predominantly by Mycobacterium tuberculosis (Mtb). It was responsible for approximately 1.4 million deaths worldwide in 2019. The lack of new drugs to treat drug‐resistant strains is a principal factor for the slow rise in TB infections. Our aim is to aid the development of new TB treatments by describing improvements (last decade, 2011–2021) to nitro(NO2)‐based compounds that have shown activity or pharmacological properties (e.g., anti‐proliferative, anti‐kinetoplastid) against Mtb. For all compounds, we have included final correlations of minimum inhibitory concentrations against Mtb (H37Rv). [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a granulomatous infection that is still the biggest cause of death across the world. TB is a leading cause of death among those living with the Human Immunodeficiency Virus (HIV) and those who have acquired immune deficiency syndrome (HIV/AIDS), accounting for one out of every three HIV deaths. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB are also on the rise, posing a major threat to global TB control efforts. And they've contributed to the situation's complexity. The emergence of MDR-TB strains demands the development of new molecular scaffolds. One possible method to combat drug resistance is to modify and reposition current anti-TB or old medications to produce derivatives that can work on resistant Mycobacterium bacilli. When compared to innovative medicines found by standard drug design and development methods, these might have a longer half-life, higher bioavailability, be more effective, and be more cost-effective. Although much research has been done on the effects of first-line drugs such as isoniazid, pyrazinamide, and rifampicin on drug-susceptible Mycobacterium tuberculosis (Mtb), little has been done on the effects of derivatives on resistant Mtb. As a result, the purpose of this research is to provide a brief overview of pyrazinamide derivatives, which have the potential to overcome resistance to the parent drug and serve as viable alternatives. Pyrazinamide derivatives' potential for developing new chemical entities (NCEs) to treat mycobacterial infections is yet unclear. [ABSTRACT FROM AUTHOR]

• Synthesis and characterization of newly synthesized thirty-one hybrids of 4-aminosalicylic acid. • in vitro evaluation of antimycobacterial and anti-inflammatory properties. • Two new compounds 16a and 16b are proposed as potential lead compounds for the discovery of dual anti-inflammatory and anti-TB drug candidates. • Computational docking simulations and in silico ADME/pharmacokinetic studies for the most active hybrids have been discussed and SAR was explored. Studies point toward a beneficial effect of NSAIDs as an adjunctive tuberculosis treatment. To discover new antitubercular compounds with anti-inflammatory activity and favorable safety profiles, three new series of non-carboxylic 4-aminosalicylic acid hybrids bearing various hydrazides (3 and 5), heterocyclic scaffolds (6 – 15), hydrazones (16a – d) and carboxylic analogues bearing 1,2,3-triazoles (19 and 20), were synthesized. The synthesized hybrids were evaluated for their antimycobacterial activity against H 37 Rv using MABA assay. Among them, compounds 8, 16a–c, 19 and 20 exhibited MIC values (9.90–37.62 µM) with good selectivity index. 16b and 20 were the most potent with MIC 9.90 and 11.40 µM, respectively. Based on an in silico docking study at COX-2 active site, 11 compounds 13a, 13b, 14a–g, 16a and 16b were selected for testing their COX-2 inhibition. The most active compounds, 13a, 16a and 16b were further tested for COX-1 and 5-LOX inhibition. Also, their COX-2 selectivity indices (SI) were determined. 16a and 16b showed the highest potency and selectivity against COX-2 IC 50 = 0.31, 1.26 µg/mL, respectively, and 5-LOX with IC 50 = 5.49, 25.44 µg/mL, respectively. Computational docking simulations and in Silico ADME/pharmacokinetic studies for the most active hybrids were performed and discussed. Thus structure-activity relationships were explored. In conclusion, compounds 16a and 16b represent a good starting point for the development of new potential drugs of dual antitubercular and anti-inflammatory activities. [Display omitted] [ABSTRACT FROM AUTHOR]

• Compounds 7f and 7i exhibited potent antibacterial activity with MIC 1 and 0.5 µg/mL against S. aureus , respectively. • compound 17b exhibited MIC value of 1 µg/mL against M. tuberculosis and drug resistant strains of Mtb. • Nontoxic to Vero cells (CC 50 (>25)) and favorable selectivity index ((S.I.) > 12.5). • Compounds 7f , and 7i , showed potent activity with MIC 0.5-1 µg/mL against MSSA, MRSA, and VRSA isolates. • A topoisomerase inhibition assay and in silico studies were performed to investigate the mechanism of action. The rapid rise in antimicrobial resistance (AMR) has become a major threat to human health. Consequently, the constant search for new antibacterial agents that work against resistant organisms has become a global initiative. To discover new antibacterial agents with improved efficacy and activity against drug-resistant organisms, we designed and synthesized a series of new naphthalimide-coumarin hybrids and evaluated them for their antimicrobial activity against a panel of bacterial and mycobacterial strains. In the preliminary evaluation, compounds 7a, 7c, 7d, 7e, 7f, 7 h, 7i, 7o, 7q, 20a and 20b exhibited potent inhibitory activity against S. aureus ATCC 29213 with MICs in the range of 0.5–32 µg/mL. Compounds 7c, 7d, 7f, 7 h, 7i, 7o, 20a, and 20b also exhibited good inhibitory activity against S. epidermidis with MIC 1–16 µg/mL. All these compounds were found to be non-toxic to Vero cells (CC 50 = >50) and exhibited a favorable selectivity index (SI = >12.5). Additionally, these compounds 7c, 7d, 7e, 7f, 7 h, 7i, 7o, 20a and 20b have shown potent inhibition against various multidrug-resistant strains of S. aureus, including VRSA with MICs in the range of 0.5–16 µg/mL. Interestingly, compound 17b showed potent antimycobacterial activity against M. tuberculosis H37Rv with MIC 1 µg/mL and a favorable selectivity index. It also exhibited potent inhibitory activity against DR-Mtb with MIC 1 µg/mL. Topoisomerase enzyme inhibition assay was carried out to validate the mechanism of action. Furthermore, in silico studies were performed to investigate the binding mode and interactions at the active site of the target enzyme. These results highlight the potential of naphthalimide-coumarin hybrids as novel antimicrobial agents. [Display omitted] [ABSTRACT FROM AUTHOR]

Recently, imidazooxazines have attracted more attention due to their therapeutic potential against tuberculosis (TB). The present study aimed to identify and develop potential inhibitors against Pks13-TE to combat the antimicrobial drug resistance of TB. Computer-aided drug design is a more highly valued technology than the traditional drug discovery approach. Herein, we computationally investigated a chemical dataset using QSAR models and virtually screened novel leads of imidazooxazines against the thioesterase domain, further subjecting them to molecular docking and dynamics simulation. The present study identified two molecules, 1 and 3, promising leads with minimum energy conformations of −7.63 and −7.62 kcal, respectively, providing structural insight into Pks13 inhibition. The average values of MolSA, SASA, and PSA for molecules 1 and 3 were 382.41 Å, 77.65 Å, and 195.54 Å and 386.24 Å, 71.105 Å, and 184.46 Å, respectively. In conclusion, our research has demonstrated that imidazoxazines are promising leads to combat the resistance problem of TB. Among the two potent molecules 1 and 3, molecule 1 displayed favourable interactions in the active site with good stability, as confirmed by the RMSD, RMSF, RoG, H-bond, and SASA analyses. The Molecule 1 protein complex showed two strong hydrogen bonds, effectively maintained for 80–85 % of the simulation time, indicating its stability and potency. The identified two molecules and their conformations were highly stable; hence, these findings provide valuable insight into the evolution of new therapeutic agents to address the growing problem of TB and its resistance. [ABSTRACT FROM AUTHOR]