Rosmarinic acid and its derivative's duel as antitubercular agents: insights from computational prediction to functional response in vitro.

Tuberculosis is one of the most dreadful infectious diseases, afflicting global populations with anguish. With the emergence of multi-drug resistant strains of mycobacteria, the imperative for new anti-tuberculosis drugs has grown exponentially. Thus, the current study delves into evaluating the impact of Perovskia abrotanoides and its active metabolites-namely, rosmarinic acid and its derivatives-against strains of Mycobacterium tuberculosis (Mtb). Through the use of the CRI assay, the antimycobacterial potential of the high-altitude medicinal plant P. abrotanoides was gauged, while docking and molecular dynamics simulations unveiled plausible targets. Of these, the peak antimycobacterial effectiveness was observed in the P. abrotanoides ethyl acetate extract with 125 µg/mL as minimum inhibitory concentration against various strains of M. tuberculosis, encompassing H37Rv and strains resistant to multiple drugs. Following bioassay-guided fractionation and isolation, rosmarinic acid and rosmarinic acid methyl ester emerged as potent molecules against H37Rv and multidrug-resistant M. tuberculosis strains; minimum inhibitory concentration ranging from 15 to 32 µg/mL. Additionally, out of 22 targets explored, Mtb lipoamide dehydrogenase (PDB: 3II4) and Rv2623 (PDB: 3CIS) were forecasted as potential Mtb targets for rosmarinic acid and rosmarinic acid methyl ester, respectively, a supposition further affirmed by molecular simulations (100 ns). The stability of both complexes throughout the simulation was measured by protein backbone root-mean-square deviation, substantiating their roles as respective targets for antimycobacterial activities.Communicated by Ramaswamy H. Sarma.

Development of an App for Tracking Family Engagement With Early Intervention Services: Focus Groups and Pilot Evaluation Study.

BACKGROUND: Expedient access to early intervention (EI) systems has been identified as a priority for children with developmental delays, identified disabilities, and other special health care needs. Despite the mandated availability of EI, it remains challenging for families to navigate referral processes and establish appropriate services. Such challenges disproportionately affect families from traditionally underserved communities. Mobile health apps can improve clinical outcomes, increase accessibility to health services, and promote adherence to health-related interventions. Though promising, the implementation of apps within routine care is in its infancy, with limited research examining the components of what makes an effective app or how to reach families most impacted by inequities in health care delivery. OBJECTIVE: In study 1, we conducted focus groups to access a broad range of perspectives on the process of navigating the EI system, with the dual goals of identifying ways in which a patient-facing app might facilitate this process and identifying barriers to use with traditionally underrepresented and underserved groups. In study 2, focus group findings informed the development of a patient-facing app, which was subsequently tested with a pilot sample of 5 families. METHODS: In study 1, the focus groups included 29 participants from 4 shareholder groups. Targeted sampling was used to recruit participants from traditionally underrepresented groups. Focus group questions sought information about barriers families experience as they navigate the EI system, ideal features of a patient-facing app designed to track family engagement with the EI system, and potential barriers. Focus group procedures were informed by the Consolidated Framework for Implementation Research framework. In study 2, a pilot app was developed. The app was tested with a sample of 5 families of young children involved in the EI system. Families provided information on app functionality and usability. RESULTS: Qualitative analysis revealed a desire for increased communication and information about the process of accessing EI services, potential utility of an app for communication purposes, and clear recommendations for app features. Insights from focus groups were used to inform the development of the Family on Track app and related implementation supports. App features included survey customization, timing and delivery of prompts, and questions related to barriers and service satisfaction. Implementation supports include a visual guide for app installation, resources related to common family questions, and availability of study personnel to guide families through installation and provide ongoing support. Field testing provided preliminary information about app usability, including identifying future directions. CONCLUSIONS: The results of this study could support the development of a new way for the EI system to communicate and connect with families, provide families with a means to communicate satisfaction and frustration, and access the supports they need to be active participants in their child's care.

The Potential of Mur Enzymes as Targets for Antimicrobial Drug Discovery.

The extensive development in the strains of resistant bacteria is a potential hazard to public health worldwide. This necessitates the development of newer agents with the antibacterial property having new mechanisms of action. Mur enzymes catalyze the steps related to the biosynthesis of peptidoglycan, which constitutes a major part of the cell wall in bacteria. Peptidoglycan increases the stiffness of the cell wall, helping it to survive in unfavorable conditions. Therefore, the inhibition of Mur enzymes may lead to novel antibacterial agents that may help in controlling or overcoming bacterial resistance. Mur enzymes are classified into MurA, MurB, MurC, MurD, MurE, and MurF. Until-date, multiple inhibitors are reported for each class of the Mur enzymes. In this review, we have summarized the development of Mur enzyme inhibitors as antibacterial agents in the last few decades.

Pyridine: the scaffolds with significant clinical diversity.

The nitrogen-bearing heterocycle pyridine in its several analogous forms occupies an important position as a precious source of clinically useful agents in the field of medicinal chemistry research. This privileged scaffold has been consistently incorporated in a diverse range of drug candidates approved by the FDA (Food and Drug Administration). This moiety has attracted increasing attention from several disease states owing to its ease of parallelization and testing potential pertaining to the chemical space. In the next few years, a larger share of novel pyridine-based drug candidates is expected. This review unifies the current advances in novel pyridine-based molecular frameworks and their unique clinical relevance as reported over the last two decades. It highlights an inclination to the use of pyridine-based molecules in drug crafting and the subsequent emergence of several potent and eligible candidates against a range of diversified diseases.

Anti-mycobacterial Constituents from Medicinal Plants; A Review.

Effective treatment of tuberculosis has been hampered by the emergence of drug-resistant strains of Mycobacterium therapeutic facilities tuberculosis. With the global resurgence of tuberculosis with the development of multidrug-resistant cases, there is a call for the development of new drugs to combat these diseases. Throughout history, natural products have afforded a rich source of compounds that have found many applications in the fields of medicine, pharmacy and biology, and continued to play a significant role in the drug discovery and development process. This review article depicts the various potential plant extracts as well as plant derived phytoconstituents against the H37rv, the most persistent strains of Mycobacterium tuberculosis and its multidrug strains.

Evaluation of antimycobacterial, leishmanicidal and antibacterial activity of three medicinal orchids of Arunachal Pradesh, India.

BACKGROUND: The ethnic population of Arunachal Pradesh uses a number of orchids as such, or in decoction for various ailments. Three untapped orchids namely, Rhynchostylis retusa, Tropidia curculioides and Satyrium nepalense, traditionally used in tuberculosis, asthma and cold stage of malaria in folk medicine, were selected for the present study. METHODS: Dried material of each plant was divided into three parts. Solvent extraction and fractionation afforded altogether 30 extracts and fractions, which were evaluated against Mycobacterium tuberculosis (H37Rv and MDR strain) for antimycobacterial activity; promastigotes and amastigotes of Leishmania donovani for leishmanicidal activity and two gram positive and three gram negative clinical isolates for antibacterial activity. RESULTS: The most significant antimycobacterial activity was observed with n-hexane fraction of the flower of Satyrium nepalense with MIC of 15.7 µg/mL. The most promising leishmanicidal activity was observed with diethyl ether fraction of the roots of Rhynchostylis retusa with IC50 values of 56.04 and 18.4 µg/mL against promastigotes and intracellular amastigotes respectively. Evaluation of antibacterial activity identified S. nepalense flower n-hexane and R. retusa roots diethyl ether as potential fractions with MIC values of ≤100 µg/mL against selected clinical isolates. CONCLUSIONS: This is the first report of the plants possessing antimycobacterial and leishmanicidal activity. The investigation resulted in identification of S. nepalense as the most promising plant, which possessed all three activities in significant proportion. This laboratory outcome could be translated to marketable pharmaceutical products and also to produce maximum benefits to the local of nearby area. Antimycobacterial and leishmanicidal activity of medicinal orchids.

Bioassay guided screening, optimization and characterization of antioxidant compounds from high altitude wild edible plants of Ladakh.

Seven edible plants including three unexplored species of high altitude (Ladakh) region were screened for antioxidant activity by bioassay guided fractionation method. The objective of the study was to dereplicate the complex phytochemical matrix of a plant in reference to antioxidant activity in vitro. The screening result showed that ethylacetate fraction of Nepeta longibracteata possesses maximum antioxidant activity, comparable to that of green tea. It also exhibited significant protecting effect against oxidative stress induced by t-BHP in human RBCs. Phytochemical profiling of the most active fraction by nontargeted RP-HPLC-MS and MS/MS technique showed that rosmarinic acid and methylrosmarinate constituted nearly 51 % of the total metabolites apart from twelve other major chemotypes.