Air Induced Phosphoryl Radical Mediated Stereoselective Hydrosulfonylation of Alkynes via Halogen Atom Transfer: Ingress of Z-Vinyl Sulfones.

The phosphoryl radical is well-known to participate in addition reactions with alkenes/alkynes. Here, we report a novel reaction mode of the phosphoryl radical where it participates in halogen atom transfer (XAT) with electron deficient vinyl halides instead of a facile addition reaction. Nevertheless, in comparison with aryl and alkyl halides, the exploitation of vinyl halides into a carbon radical via XAT is quite rare. This protocol provides an opportunity for direct hydrosulfonylation of numerous internal as well as terminal alkynes to get various Z-vinyl sulfones under environmentally benign conditions. Generation of the phosphoryl radical in the open air, water as a solvent, excellent functional group compatibility, and exceptional chemoselectivity are the attractive features of the present methodology.

Bloqueo ecoguiado del nervio obturador al nivel de la rama púbica superior: estudio en cadáver embalsamado en Thiel utilizando látex / Sonographic obturator nerve block at level of superior pubic ramus: A Thiel based cadaveric investigation with latex

Introducción: El bloqueo del nervio obturador proximal tiene una eficacia similar al bloqueo del nervio obturador distal. Los estudios en cadáveres previos que inyectaban azul de metileno y realizaban seguidamente la disección reflejaron que la solución se dispersa a las divisiones anterior y posterior del nervio obturador, en el punto de salida del canal obturador. La absorción de azul de metileno por parte de la fascia y los músculos oscurece la delineación exacta de los nervios teñidos. Nosotros conjeturamos que la inyección de látex al nivel de las ramas púbicas superiores en el plano entre los músculos pectíneo y obturador externo mediante guía ecográfica a tiempo real, seguida de disección demorada en un cadáver embalsamado en Thiel, sería la técnica óptima de investigación en cadáveres. Métodos: Obtuvimos 3 cuerpos donados a la ciencia (BDTS) conforme a las normas estrictas del programa de donación del Departamento de Anatomía Macroscópica y Clínica de la Universidad de Medicina de Graz, y a la normativa sobre enterramientos de Estiria. Los BDTS fueron embalsamados utilizando el método de Thiel, que aporta condiciones muy realistas para las investigaciones con anestesia regional. En 2 cadáveres, las inyecciones de látex se realizaron de forma ecoguiada, y en el tercero se realizaron secciones transversales. Resultados: Nuestras disecciones abiertas de los cadáveres embalsamados en Thiel (C1 y C2) reflejaron que la inyección única de látex en el plano interfascial entre los músculos pectíneo y obturador externo al nivel de la rama púbica superior originó una dispersión adecuada a lo largo del tronco del nervio obturador y sus ramas, en todas las muestras. Conclusiones: La inyección ecoguiada de látex dentro del plano al nivel de las ramas púbicas superiores entre los músculos pectíneo y obturador externo cubre las ramas anterior y posterior y el tronco del nervio obturador.(AU)

Introduction: A proximal obturator nerve block has a similar block efficacy as the distal obturator nerve block. Previous cadaveric investigation injecting methylene blue dye solution and an immediate dissection proved the solution engulfing the anterior and posterior divisions of the obturator nerve as they emerge from the obturator canal. Uptake of methylene blue dye by the fascia and muscles obscures the exact delineation of the stained nerves. We hypothesized that injection of latex at the level of superior pubic rami in the plane between pectineus and obturator externus under real time ultrasound and a delayed dissection in a Thiel-based cadaver would be the optimal cadaveric investigational technique. Methods: Three investigated bodies donated to science (BDTS) fall under the strict rules of the donation program of the Department of Macroscopic and Clinical Anatomy of the Medical University of Graz and the Styrian burial law. The BDTS were embalmed with Thieĺs method which provides very lifelike conditions for investigations with regional anaesthesia backgrounds. In two cadavers (a total of specimens), latex injections were performed under ultrasound, while in the third cadaver cross-sections were executed. Results: Our Thiel based cadaveric open dissection (C1 and C2) demonstrated that a single injection of latex in the inter-fascial plane between the pectineus muscle and the obturator externus muscle at the level of superior pubic ramus led to adequate spread along trunk of the obturator nerve and its branches in all specimens. Conclusions: An in-plane ultrasound-guided latex injections at the level of superior pubic rami, between the pectineus and the obturator externus muscles soaks the anterior ramus, posterior ramus, and the obturator nerve trunk.(AU)

An optimized Nurr1 agonist provides disease-modifying effects in Parkinson's disease models.

The nuclear receptor, Nurr1, is critical for both the development and maintenance of midbrain dopamine neurons, representing a promising molecular target for Parkinson's disease (PD). We previously identified three Nurr1 agonists (amodiaquine, chloroquine and glafenine) that share an identical chemical scaffold, 4-amino-7-chloroquinoline (4A7C), suggesting a structure-activity relationship. Herein we report a systematic medicinal chemistry search in which over 570 4A7C-derivatives were generated and characterized. Multiple compounds enhance Nurr1's transcriptional activity, leading to identification of an optimized, brain-penetrant agonist, 4A7C-301, that exhibits robust neuroprotective effects in vitro. In addition, 4A7C-301 protects midbrain dopamine neurons in the MPTP-induced male mouse model of PD and improves both motor and non-motor olfactory deficits without dyskinesia-like behaviors. Furthermore, 4A7C-301 significantly ameliorates neuropathological abnormalities and improves motor and olfactory dysfunctions in AAV2-mediated α-synuclein-overexpressing male mouse models. These disease-modifying properties of 4A7C-301 may warrant clinical evaluation of this or analogous compounds for the treatment of patients with PD.

Mesoporous Copper-Magnesium Oxide Hybrid Nanocatalyzed Synthesis of 3-Substituted Isocoumarins from 2-Iodobenzoic Acid and Terminal Alkyne under Green Conditions.

A 3-substituted isocoumarin scaffold has captivated extensive interest in synthetic and medicinal chemistry due to its presence in various natural products with diverse biological activities. Herein, we report a mesoporous CuO@MgO nanocomposite that was prepared via the sugar-blowing induced confined method with an E-factor of 12.2 and its catalytic potential in the facile synthesis of 3-substituted isocoumarin from 2-iodobenzoic acids and terminal alkynes. Powder X-ray diffraction, scanning electron microscopy, high-resolution transmission electron microscopy, energy-dispersive X-ray analysis, X-ray photoelectron spectroscopy, and Brunauer-Emmett-Teller techniques were utilized for the characterization of the as-prepared nanocomposite. A broad substrate scope, mild reaction conditions, excellent yield in short reaction time, no usage of additives, and better green chemistry metrices such as a low E-factor (0.71), high reaction mass efficiency (58.28%), low process mass efficiency (1.71), and high turnover number (629) are the various advantages of the present synthetic route. The nanocatalyst was recycled and reused up to five runs without significant loss in its catalytic activity and a very low leaching of copper (3.20 ppm) and magnesium ions (0.72 ppm). Powder X-ray diffraction and high-resolution transmission electron microscopy techniques confirmed the structural integrity of the recycled CuO@MgO nanocomposite.

Regiodivergent Synthesis of Densely Functionalized Indolizines via (2 + 2 + 1) Cycloaddition.

A novel metal and additive free, atom-economic method for the regiodivergent synthesis of crucial 6- or 8-substituted indolizine from meta-amide-substituted pyridine and alkyne via a [2 + 2 + 1] cycloaddition is developed. The reaction proceeds through the cleavage of the carbon-carbon triple bond. The synthesized product contains an important amide group that can be further functionalized to afford biologically active compounds.

Bloqueo ecoguiado bajo el músculo multífido para el dolor postoperatorio tras cirugía de columna lumbar: serie prospectiva de casos / Ultrasound-guided sub-multifidus block for postoperative pain after lumbar spine surgery — a prospective case series

Describimos esta serie de 15casos programados para descompresión de columna lumbar a un único nivel con instrumental, en la que practicamos bloqueo ecoguiado bajo el músculo multífido (SMFB). Se inyectó el anestésico local en profundidad hacia el músculo multífido logrando el bloqueo seguro de las ramas dorsales de los nervios espinales a múltiples niveles en esta serie. Con ultrasonidos (US) puede identificarse el músculo multífido en los planos axial y parasagital. La punta de la aguja se visualiza fácilmente bajo el músculo multífido y en posición medial hacia el proceso transverso. Se documentó la buena calidad de la analgesia utilizando las puntuaciones para el dolor. No se produjeron episodios adversos. Este bloqueo debe compararse con la analgesia multimodal rutinaria o el bloqueo en el plano interfascial del músculo toracolumbar recientemente descrito, en términos de seguridad y eficacia analgésica.(AU)

We describe a series of 15 patients scheduled for single level lumbar spine decompression with instrumentation receiving ultrasound (US) guided submultifidus block (SMFB). In this series, injections of local anesthetic deep to the multifidus muscle provided reliable block of dorsal rami of spinal nerves at multiple levels. With US, the multifidus muscle can be identified both in axial and parasagittal planes. Needle tip is easily visualized beneath the multifidus and medial to the transverse process. Good quality analgesia was documented by pain scores. There were no adverse events. Further studies are needed to compare this nerve block with routine multimodal analgesia or with the recently described thoracolumbar interfascial plane block to compare safety and analgesic efficacy.(AU)

Ultrasound-guided sub-multifidus block for postoperative pain after lumbar spine surgery - a prospective case series.

We describe this series of 15 cases who were scheduled for single level lumbar spine decompression with instrumentation. Here we describe ultrasound (US) guided sub-multifidus block (SMFB). Injections of local anesthetic deep to the multifidus muscle provided reliable block of dorsal rami of spinal nerves at multiple levels in this series. With US the multifidus muscle can be identified both in axial and parasagittal planes. Needle tip is easily visualized beneath the multifidus and medial to transverse process. A good quality analgesia was documented by pain scores. There were no adverse events. This block needs to be compared with routine multimodal analgesia or with the recently describe thoracolumbar interfascial plane block to compare safety and analgesic efficacy.

NSC19723, a Thiacetazone-Like Benzaldehyde Thiosemicarbazone Improves the Efficacy of TB Drugs In Vitro and In Vivo.

The complexity and duration of tuberculosis (TB) treatment contributes to the emergence of drug resistant tuberculosis (DR-TB) and drug-associated side effects. Alternate chemotherapeutic agents are needed to shorten the time and improve efficacy of current treatment. In this study, we have assessed the antitubercular activity of NSC19723, a benzaldehyde thiosemicarbazone molecule. NSC19723 is structurally similar to thiacetazone (TAC), a second-line anti-TB drug used to treat individuals with DR-TB. NSC19723 displayed better MIC values than TAC against Mycobacterium tuberculosis and Mycobacterium bovis BCG. In our checkerboard experiments, NSC19723 displayed better profiles than TAC in combination with known first-line and recently approved drugs. Mechanistic studies revealed that NSC19723 inhibits mycolic acid biosynthesis by targeting the HadABC complex. Computational studies revealed that the binding pocket of HadAB is similarly occupied by NSC19723 and TAC. NSC19723 also improved the efficacy of isoniazid in macrophages and mouse models of infection. Cumulatively, we have identified a benzaldehyde thiosemicarbazone scaffold that improved the activity of TB drugs in liquid cultures, macrophages, and mice. IMPORTANCE Mycobacterium tuberculosis, the causative agent of TB is among the leading causes of death among infectious diseases in humans. This situation has worsened due to the failure of BCG vaccines and the increased number of cases with HIV-TB coinfections and drug-resistant strains. Another challenge in the field is the lengthy duration of therapy for drug-sensitive and -resistant TB. Here, we have deciphered the mechanism of action of NSC19723, benzaldehyde thiosemicarbazone. We show that NSC19723 targets HadABC complex and inhibits mycolic acid biosynthesis. We also show that NSC19723 enhances the activity of known drugs in liquid cultures, macrophages, and mice. We have also performed molecular docking studies to identify the interacting residues of HadAB with NSC19723. Taken together, we demonstrate that NSC19723, a benzaldehyde thiosemicarbazone, has better antitubercular activity than thiacetazone.

Design and synthesis of benzimidazole derivatives as antimycobacterial agents.

A series of 2,5-disubstituted benzimidazole derivatives was synthesized with the aim to identify compounds with potent anti-TB activity. All the compounds were screened in vitro against cultured Mycobacterium tuberculosis H37 Rv strain and found to be exhibiting MIC99 values in the range of 0.195-100 µM. Out of 43 synthesized compounds, two compounds 11h and 13e showed better anti-TB activity than the reference drug isoniazid.

Dissecting The role of Plasmodium metacaspase-2 in malaria gametogenesis and sporogony.

The family of apicomplexan specific proteins contains caspases-like proteins called "metacaspases". These enzymes are present in the malaria parasite but absent in human; therefore, these can be explored as potential drug targets. We deleted the MCA-2 gene from Plasmodium berghei genome using a gene knockout strategy to decipher its precise function. This study has identified that MCA-2 plays an important role in parasite transmission since it is critical for the formation of gametocytes and for maintaining an appropriate number of infectious sporozoites required for sporogony. It is noticeable that a significant reduction in gametocyte, oocysts, ookinete and sporozoites load along with a delay in hepatocytes invasion were observed in the MCA-2 knockout parasite. Furthermore, a study found the two MCA-2 inhibitory molecules known as C-532 and C-533, which remarkably inhibited the MCA-2 activity, abolished the in vitro parasite growth, and also impaired the transmission cycle of P. falciparum and P. berghei in An. stephensi. Our findings indicate that the deletion of MCA-2 hampers the Plasmodium development during erythrocytic and exo-erythrocytic stages, and its inhibition by C-532 and C-533 critically affects the malaria transmission biology.

Monocarbonyl curcuminoids as antituberculosis agents with their moderate in-vitro metabolic stability on human liver microsomes.

Tuberculosis, an airborne infectious disease, results in a high morbidity and mortality rate. The continuous emergence of TB resistance strains including MDR (multidrug-resistant tuberculosis), XDR (extensive drug-resistant tuberculosis), and especially TDR (totally drug-resistant tuberculosis) is a major public health threat and has intensified the need to develop new antitubercular agents. A natural product, curcumin, possesses diverse biological activities but suffers due to a lack of water solubility and bioavailability. To overcome these limitations, a series of 17 water-soluble monocarbonyl curcuminoids was synthesized and evaluated for antimycobacterial activity. All compounds exhibited good to moderate anti-TB activity with MIC99 in the range of 3.12-25.0 µM, out of which 7c and 7p were found the most potent compounds with MIC99 in the range of 3.12-6.25 µM. Furthermore, these compounds were observed to be nonhaemolytic, nontoxic, and stable under both physiological as well as reducing conditions. In-vitro metabolic stability data of the representative compound 7p with the human liver microsome revealed that these compounds possess a moderate metabolism with a half-life of 1.2 h and an intrinsic clearance of 1.12 ml/h/mg.

Site-directed mutagenesis in the P-domain of calreticulin transacylase identifies Lys-207 as the active site residue.

In silico-docking studies from previous work have suggested that Lys-206 and lys-207 of calreticulin (CR) play a pivotal key role in its well-established transacetylation activity. To experimentally validate this prediction, we introduced three mutations at lysine residues of P-domain of CR: K → A, P mut-1 (K -206, -209), P mut-2 (K -206, -207) and P mut-3 (K -207, -209) and analyzed their immunoreactivity and acetylation potential. The clones of wild-type P-domain (P wt ) and three mutated P-domain (P mut-1, P mut-2 and P mut-3) were expressed in pTrcHis C vector and the recombinant P wt , P mut-1 , P mut-2 and P mut-3 proteins were purified by Ni-NTA affinity chromatography. Screening of the transacylase activity (TAase) by the Glutathione S Transferase (GST) assay revealed that the TAase activity was associated with the P wt and P mut-1 while P mut-2 and P mut-3 did not show any activity. The immune-reactivity to anti-lysine antibody was also retained only by the P mut-1 in which the Lys-207 was intact. Retention of the TAase activity and immunoreactivity of P mut-1 with mutations introduced at Lys-206, Lys-209, while its loss with a mutation at Lys-207 residue indicated that lysine-207 of P-domain constitutes the active site residue controlling TAase activity. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02659-1.

QcrB in Mycobacterium tuberculosis: The new drug target of antitubercular agents.

Drug-resistance in mycobacterial infections is a major global health problem that leads to high mortality and socioeconomic pressure in developing countries around the world. From finding new targets to discovering novel chemical scaffolds, there is an urgent need for the development of better approaches for the cure of tuberculosis. Recently, energy metabolism in mycobacteria, particularly the oxidative phosphorylation pathway of cellular respiration, has emerged as a novel target pathway in drug discovery. New classes of antibacterials which target oxidative phosphorylation pathway either by interacting with a protein or any step in the pathway of oxidative phosphorylation can combat dormant mycobacterial infections leading to shortening of tuberculosis chemotherapy. Adenosine triphosphate synthase is one such recently discovered target of the newly approved antitubercular drug bedaquiline. Cytochrome bcc is another new target of the antitubercular drug candidate Q203, currently in phase II clinical trial. Research suggests that b subunit of cytochrome bcc, QcrB, is the target of Q203. The review article describes the structure, function, and importance of targeting QcrB throwing light on all chemical classes of QcrB inhibitors discovered to date. An understanding of the structure and function of validated targets and their inhibitors would enable the development of new chemical entities.

3D QSAR studies on amphiphilic indoles for antimycobacterial activity.

A persistent infection prolongs treatment duration and also enhances the chance of resistance development against antibiotics. Recently, a class of amphiphilic indole derivatives was discovered exhibiting bactericidal activity against both growing and nongrowing Mycobacterium bovis BCG (M. bovis BCG). These antibacterials are suggested to disturb the integrity and functioning of the cell membrane, a property that can help eradicate persistent organisms. This study article describes field-based three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of 79 amphiphilic indole derivatives. The aim of this QSAR study is to optimize this class of compounds for the development of more potent antimycobacterial agents. The results obtained indicate that steric interactions are crucial for antimycobacterial activity, while hydrogen bond donor groups participate negligibly in activity. The derived 3D-QSAR models showed acceptable r2 (0.91) and q2 (0.91) with a root mean squared error (RMSE) of 0.08. The models were cross-validated using the leave-one-out method. Applying the same QSAR model to another congeneric series of amphiphilic indoles externally validated the QSAR model. The model could appreciably predict the activity (pMIC50 ) of this congeneric series of amphiphilic indoles, with an RMSE of 0.49, indicating the robustness of the model and its efficiency in predicting the potentially active compounds.

Synthesis of novel monocarbonyl curcuminoids, evaluation of their efficacy against MRSA, including ex vivo infection model and their mechanistic studies.

In continuation of our effort to improve the physiological stability and the antibacterial activity of curcuminoids against drug-resistant bacteria, a series of novel monocarbonyl curcuminoids were synthesized and screened for antibacterial activity against S. aureus and E. coli strains. These curcuminoids showed potent antibacterial activity against both methicillin-sensitive and methicillin-resistant strains of S. aureus with MIC values 2-8 and 4-16 µg/mL, respectively. They also exhibited moderate potency against E. coli strains. The four most active curcuminoids (7d, 7i, 7m, and 7p) were on further investigation found to be very stable under physiological conditions, non-hemolytic, and non-toxic toward mammalian cells up to 150 µg/mL concentration. Mechanistic studies revealed that these curcuminoids displayed potent bactericidal activity by targeting cell membranes. Further, in an ex vivo mammalian co-culture infection model study, remarkably, the curcuminoids 7i and 7p were able to clear the internalized bacteria in mammalian cells and the activity was found to be superior to conventional antibiotics such as vancomycin and linezolid. Therefore, the present study affords us water-soluble, stable, non-toxic curcuminoids that may serve as lead molecules for development as antibacterial agents against MRSA infections.

Bilateral erector spinae plane block for scoliosis surgery: Case series. / Bloqueo bilateral en el plano del músculo erector de la columna para cirugía de escoliosis: serie de casos.

Spinal correction surgery is a very invasive surgical procedure and results in severe postoperative pain. We report six cases in which Bilateral Erector Spinae Plane Block was performed for scoliosis surgery. Our aim was to provide an effective perioperative pain management and to achieve intraoperative hemodynamic stability with no interference on neuromonitoring. The technical challenges are also highlighted. An ultrasound guided scout scan is necessarry to identify the bony prominences and determine the possible multiple injection points. Erector Spinae Plane Block in scoliosis surgery is an easier and safer technique compared to epidural anesthesia and can use instrumented complex spinal surgery. This block seems to have a role in perioperative pain pathway complementing the multimodal analgesic regimen and not have interference with evocated potentials in adults. However the diffusion mechanism of the this block is not well known hence it should be awake regarding local anesthetic toxicity.

An overview of new antitubercular drugs, drug candidates, and their targets.

The causative agent of tuberculosis (TB), Mycobacterium tuberculosis and more recently totally drug-resistant strains of M. tuberculosis, display unique mechanisms to survive in the host. A four-drug treatment regimen was introduced 40 years ago but the emergence of multidrug-resistance and more recently TDR necessitates the identification of new targets and drugs for the cure of M. tuberculosis infection. The current efforts in the drug development process are insufficient to completely eradicate the TB epidemic. For almost five decades the TB drug development process remained stagnant. The last 10 years have made sudden progress giving some new and highly promising drugs including bedaquiline, delamanid, and pretomanid. Many of the candidates are repurposed compounds, which were developed to treat other infections but later, exhibited anti-TB properties also. Each class of drug has a specific target and a definite mode of action. These targets are either involved in cell wall biosynthesis, protein synthesis, DNA/RNA synthesis, or metabolism. This review discusses recent progress in the discovery of newly developed and Food and Drug Administration approved drugs as well as repurposed drugs, their targets, mode of action, drug-target interactions, and their structure-activity relationship.

Development of Magnesium Oxide-Silver Hybrid Nanocatalysts for Synergistic Carbon Dioxide Activation to Afford Esters and Heterocycles at Ambient Pressure.

Multi-metallic hybrid nancatalysts consisting of a porous metal oxide host and metal satellite guests serve as a scaffold for multi-step transformations of divergent and energy-challenging substrates. Here we have developed a 3D porous MgO framework (Lewis basic host) with Ag0 nanoparticles (noble metal guest) for ambient pressure activation and insertion of CO2 into unsaturated alkyne substrates. The hybrid MgO@Ag-x (x = 2, 5, 7, 8 at % Ag) catalysts are synthesized by impregnating Ag+ ions in porous MgO cubes followed by reduction using NaBH4. Morphological (SEM, TEM, EDX mapping) and structural (PXRD, XPS) characterization reveal that the micron-sized hybrid cubes derive from self-assembly of ~100 nm (edge length) MgO cubes decorated with ~ 5 to 25 nm Ag0 NPs. Detailed XPS analysis illustrates Ag0 is present in two forms, <10 nm NPs and ~25 nm aggregates. The MgO@Ag-7 catalyst is effective for inserting CO2 into aryl alkynes followed by SN2 coupling with allylic chlorides to afford a wide range of ester and lactone heterocycles in excellent yields (61-93%) and with low E-factor (2.8). The proposed mechanism suggests a CO2 capture and substrate assembly role for 3D porous MgO while Ag0 performs the key activation of alkyne and CO2 insertion steps. The catalyst is recyclable (5x) with no significant loss of product yield. Overall, these results demonstrate viable approaches to hybrid catalyst development for challenging conversions such as CO2 utilization in a green and sustainable manner.

Hybridization of Fluoro-amodiaquine (FAQ) with Pyrimidines: Synthesis and Antimalarial Efficacy of FAQ-Pyrimidines.

To evade the possible toxicity associated with the formation of quinone-imine metabolite in amodiaquine (AQ), the para-hydroxyl group was replaced with a -F atom, and the resulting 4'-fluoro-amodiaquine (FAQ) was hybridized with substituted pyrimidines. The synthesized FAQ-pyrimidines displayed better in vitro potency than chloroquine (CQ) against the resistant P. falciparum strain (Dd2), exhibiting up to 47.3-fold better activity (IC50: 4.69 nM) than CQ (IC50: 222 nM) and 2.8-fold better potency than artesunate (IC50: 13.0 nM). Twelve compounds exhibited better antiplasmodial activity than CQ against the CQ-sensitive (NF54) strain. Two compounds were evaluated in vivo against a P. berghei-mouse malaria model. Mechanistic heme-binding studies, computational docking studies against Pf-DHFR and in vitro microsomal stability studies were performed for the representative molecules of the series to assess their antimalarial efficacy.

NSC 18725, a Pyrazole Derivative Inhibits Growth of Intracellular Mycobacterium tuberculosis by Induction of Autophagy.

The increasing incident rates of drug-resistant tuberculosis (DR-TB) is a global health concern and has been further complicated by the emergence of extensive and total drug-resistant strains. Identification of new chemical entities which are compatible with first-line TB drugs, possess activity against DR-, and metabolically less active bacteria is required to tackle this epidemic. Here, we have performed phenotypic screening of a small molecule library against Mycobacterium bovis BCG and identified 24 scaffolds that exhibited MIC99 values of at least 2.5 µM. The most potent small molecule identified in our study was a nitroso containing pyrazole derivative, NSC 18725. We observed a significant reduction in viable bacilli load of starved Mycobacterium tuberculosis upon exposure to NSC 18725. The action of NSC 18725 was "synergistic" with isoniazid (INH) and "additive" with other drugs in our checkerboard assays. Structure-activity relationship (SAR) studies of the parent compound revealed that pyrazole derivatives without a functional group at fourth position lacked anti-mycobacterial activity in vitro. The derivative with para-chlorophenyl substitution at the first position of the pyrazole ring was the most active scaffold. We also demonstrate that NSC 18725 is able to induce autophagy in differentiated THP-1 macrophages. The induction of autophagy by NSC 18725 is the major mechanism for the killing of intracellular slow and fast-growing mycobacteria. Taken together, these observations support the identification of NSC 18725 as an antimycobacterial compound, which synergizes with INH, is active against non-replicative mycobacteria and induces autophagy in macrophages.