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Acta Biomater 2019 Apr 17. Epub 2019 Apr 17.

HIPS - Helmholtz Institute for Pharmaceutical Research Saarland, Helmholtz Centre for Infection Research (HZI), Saarland University, Universitätscampus E8.1, 66123 Saarbrücken, Germany; Department of Pharmacy, Saarland University, 66123, Saarbrücken, Germany. Electronic address:

Predictive in vitro models are valuable alternatives to animal experiments for evaluating the transport of molecules and (nano)particles across biological barriers. In this work, an improved triple co-culture of air-blood barrier was set-up, being exclusively constituted by human cell lines that allowed to perform experiments at air-liquid interface. Epithelial NCI-H441 cells and endothelial HPMEC-ST1. Read More

J Biol Chem 2019 Apr 11. Epub 2019 Apr 11.

Immunobiology, ICGEB, India.

The widespread availability and use of modern synthetic therapeutic agents have led to a massive decline in ethnomedical therapies. However, these synthetic agents often possess toxicity leading to various adverse effects. For instance, anti-tubercular treatment (ATT) is toxic, lengthy, and severely impairs host immunity, resulting in post treatment vulnerability to reinfection and reactivation of tuberculosis (TB). Read More

Curr Drug Discov Technol 2019 Apr 11. Epub 2019 Apr 11.

V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Science of Ukraine, 1 Murmanska Street, 02660, Kyiv. Ukraine.

Background: Tuberculosis (TB) is an infection disease caused by Mycobacterium tuberculosis (Mtb) bacteria. One of the main causes of mortality from TB is the problem of Mtb resistance to known drugs.

Objective: The goal of this work is to identify potent small molecule anti-TB agents by machine learning, synthesis and biological evaluation. Read More

Polymers (Basel) 2018 Jun 8;10(6). Epub 2018 Jun 8.

Centre for Biomedical Research, University of Algarve, 8005-139 Faro, Portugal.

The pulmonary delivery of antitubercular drugs is a promising approach to treat lung tuberculosis. This strategy not only allows targeting the infected organ instantly, it can also reduce the systemic adverse effects of the antibiotics. In light of that, this work aimed at producing fucoidan-based inhalable microparticles that are able to associate a combination of two first-line antitubercular drugs in a single formulation. Read More

Case Rep Pediatr 2019 5;2019:8972574. Epub 2019 Mar 5.

Obstetric and Pediatric Intensive Care Unit, Hassan II Academic Hospital, Fez, Morocco.

Isoniazid is an antimycobacterial agent commonly prescribed in most tuberculosis chemotherapy regimens. Its side effects are widely known including mainly liver toxicity and peripheral neuropathy. The toxic effects of isoniazid are dose-related. Read More

J Clin Transl Res 2018 May 28;4(1):75-100. Epub 2018 May 28.

Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, United States.

Mitochondria are critical cellular organelles for energy generation and are now also recognized as playing important roles in cellular signaling. Their central role in energy metabolism, as well as their high abundance in hepatocytes, make them important targets for drug-induced hepatotoxicity. This review summarizes the current mechanistic understanding of the role of mitochondria in drug-induced hepatotoxicity caused by acetaminophen, diclofenac, anti-tuberculosis drugs such as rifampin and isoniazid, anti-epileptic drugs such as valproic acid and constituents of herbal supplements such as pyrrolizidine alkaloids. Read More

Bioorg Med Chem 2019 Apr 21;27(8):1509-1516. Epub 2019 Feb 21.

State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210023, China. Electronic address:

A series of rhodanine derivatives RB1-RB23 were synthesized through a two-round screening. Their Mycobacterial tuberculosis (Mtb) InhA inhibitory activity and Mtb growth blocking capability were evaluated. The most potent hit compound RB23 indicated comparable InhA inhibiton (IC = 2. Read More

Int J Med Mushrooms 2019 ;21(1):29-35

Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo NSW 2007, Australia; School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW 2308, Australia and Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, Lot 1 Kookaburra Circuit, New Lambton Heights, Newcastle, NSW 2305, Australia.

Auricularia polytricha is a popular mushroom found all over the world. This article describes a study of the antiepileptic effect of A. polytricha, a mushroom that is used traditionally for treating asthma, rheumatism, tumors, cough, fever, and epilepsy, and for its antimicrobial effect. Read More

Nanomedicine (Lond) 2019 02 29;14(4):465-491. Epub 2019 Jan 29.

University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.

Aim: Evaluation of solid lipid nanoparticles (SLNs) for ocular delivery of isoniazid (INH).

Materials & Methods: INH-SLNs were characterized for morphological, thermal, crystalline and nuclear magnetic resonance properties. In vitro release and ex vivo corneal permeability of INH-SLNs was also evaluated. Read More

GMS Infect Dis 2018 9;6:Doc04. Epub 2018 Aug 9.

Department of Infectious Diseases/Center for Global Health, Dept of Public Health, Aarhus University, Denmark.

Urogenital tuberculosis (UGTB) should in general be treated as pulmonary TB with a four-drug regimen of Isoniazid, Rifampicin, Ethambutol and Pyrazinamide for a total of 6 months, Ethambutol and Pyrazinamide only the first two months. Some patients may need longer treatment (cavitary disease, kidney abscess/malfunction, HIV co-infection). Treatment of multi-drug resistant tuberculosis (MDR-TB) requires use of long-term intravenous treatment with aminoglycosides and other drugs with considerable toxicity for 18-24 months. Read More

Int J Tuberc Lung Dis 2019 Jan 20;23(1):52-57. Epub 2018 Dec 20.

Department of Clinical Pharmacology, Seth Gordhandas Sunderdas Medical College and King Edward Memorial Hospital, Mumbai, India.

Objective: To assess the pharmacokinetics of isoniazid (INH) at 10 mg/kg/day among Indian children.

Methods: INH levels were estimated using liquid chromatography-tandem mass spectroscopy in 35 children aged 1-15 years on daily anti-tuberculosis treatment. Blood samples were collected 0, 1, 2, 3, 6 and 24 h after INH administration. Read More

J Clin Transl Res 2018 28;4(1). Epub 2018 May 28.

Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, US.

Mitochondria are critical cellular organelles for energy generation and are now also recognized as playing important roles in cellular signaling. Their central role in energy metabolism, as well as their high abundance in hepatocytes, make them important targets for drug-induced hepatotoxicity. This review summarizes the current mechanistic understanding of the role of mitochondria in drug-induced hepatotoxicity caused by acetaminophen, diclofenac, anti-tuberculosis drugs such as rifampin and isoniazid, anti-epileptic drugs such as valproic acid and constituents of herbal supplements such as pyrrolizidine alkaloids. Read More

Clin Infect Dis 2018 Nov;67(suppl_3):S359-S364

Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas.

Background: One approach that could increase the efficacy and reduce the duration of antituberculosis therapy is pharmacokinetics/pharmacodynamics-based optimization of doses. However, this could increase toxicity.

Methods: We mimicked the concentration-time profiles achieved by human equivalent doses of moxifloxacin 800 mg/day, rifampin 1800 mg/day, and pyrazinamide 4000 mg/day (high-dose regimen) vs isoniazid 300 mg/day, rifampin 600 mg/day, and pyrazinamide 2000 mg/day (standard therapy) in bactericidal and sterilizing effect studies in the hollow fiber system model of tuberculosis (HFS-TB). Read More

Adv Exp Med Biol 2018;1032:15-35

Department of Biomedical Sciences, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USA.

Cytochrome P450 (P450) enzymes are involved in the metabolism of carcinogens, as well as drugs, steroids, vitamins, and other classes of chemicals. P450s also oxidize ethanol, in particular P450 2E1. P450 2E1 oxidizes ethanol to acetaldehyde and then to acetic acid, roles also played by alcohol and aldehyde dehydrogenases. Read More

Eur J Med Chem 2018 Sep 29;157:1115-1126. Epub 2018 Aug 29.

Saint Petersburg Research Institute of Phthisiopulmonology, 2-4 Ligovsky Prospekt, Saint Petersburg, 191036, Russian Federation.

Within the general nitrofuran carboxamide chemotype, chimera derivatives incorporating diversely substituted imidazoles attached via an alkylamino linker were synthesized. Antimycobacterial evaluation against drug-sensitive M. tuberculosis H37Rv strain identified five active druglike compounds which were further profiled against patient-derived M. Read More

Biochem Pharmacol 2018 Oct 25;156:340-347. Epub 2018 Aug 25.

Translational and Molecular Medicine Department, Research Center for Health Sciences and Biomedicine, Autonomous University of San Luis Potosí, Mexico; Chemical Sciences School, Autonomous University of San Luis Potosí, Mexico. Electronic address:

N-acetyltransferase 2 (NAT2) catalyzes the biotransformation of numerous arylamine and hydrazine drugs and carcinogens. Genetic polymorphisms of NAT2 modify drug efficacy and toxicity and susceptibility to diseases such as cancer and type 2 diabetes. Expression of NAT2 has been documented in the liver and gastrointestinal tract but not in other tissues. Read More

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2018 Sep;32(9):1131-1136

Department of Orthopedics, Lanzhou General Hospital of Lanzhou Military Command, Lanzhou Gansu, 730000,

Objective: To study the effect of three-dimensional (3D) printed β-tricalcium phosphate (β-TCP) scaffold loaded poly (lactide-co-glycolide) (PLGA) anti-tuberculosis drug sustained release microspheres on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and its cytotoxicity.

Methods: Isoniazid and rifampicin/PLGA sustained release microspheres were prepared by W/O/W multiple emulsion method. The β-TCP scaffolds were prepared by 3D printing technique. Read More

J Microencapsul 2018 Jun;35(4):392-405

a Centre for Biomedical Research , University of Algarve , Faro , Portugal.

Pulmonary tuberculosis accounts for 80% of cases and the delivery of antitubercular drugs into the lungs allows targeting the infected organ and, possibly, reducing systemic drug toxicity. This work aimed at using fucoidan as matrix of inhalable microparticles that associate two first-line antitubercular drugs, for an application in pulmonary tuberculosis therapy. Fucoidan is composed of fucose and sulphated sugar residues, moieties described as being recognised by surface receptors of alveolar macrophages, which host mycobacteria. Read More

Medchemcomm 2018 Jan 6;9(1):165-172. Epub 2017 Dec 6.

Academy of Scientific and Innovative Research , Indian Institute of Integrative Medicine (CSIR) , Sanatnagar , Srinagar , Jammu and Kashmir 190005 , India . Email:

Tuberculosis is an ever-evolving infectious disease that urgently needs new drugs. In the search for new antituberculosis agents, a library of 3-cinnamoyl-4-hydroxy-6-methyl-2-pyran-2-ones (CHPs) () was synthesized and evaluated against a standard virulent laboratory strain of H37Rv. Out of 25 compounds, , , and ( and ) showed least, moderate, good and appreciable activities, respectively, based on minimum inhibitory concentrations (MICs). Read More

Int J Mol Sci 2018 Aug 7;19(8). Epub 2018 Aug 7.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojarov 10, 83232 Bratislava, Slovakia.

A series of sixteen ring-substituted -arylcinnamamides was prepared and characterized. Primary in vitro screening of all the synthesized compounds was performed against , three methicillin-resistant strains, H37Ra, , and . Several of the tested compounds showed antistaphylococcal, antitubercular, and antifungal activities comparable with or higher than those of ampicillin, isoniazid, and benomyl. Read More

Pharmaceutics 2018 Jul 26;10(3). Epub 2018 Jul 26.

Laboratoire de Chimie de Coordination du CNRS, 205 Route de Narbonne, BP 44099, 31077 Toulouse CEDEX 4, France.

Tuberculosis (TB) is a contagious infection that usually attacks not only the lungs, but also brain and spine. More than twenty drugs have been developed for the treatment of TB, but most of them were developed some years ago. They are used in different combinations. Read More

J Infect 2019 Jan 24;78(1):58-65. Epub 2018 Jul 24.

General Affairs Department, Ota City Office, Tokyo, Japan. Electronic address:

Objectives: Tuberculosis (TB) is a serious infectious disease with high mortality for solid-organ transplantation. Preventive therapy of latent tuberculosis infection (LTBI) has been considered to reduce TB risk and improve outcomes of transplantation. The aim of this study was to evaluate the cost-effectiveness of the interferon-gamma release assays (IGRAs); QuantiFERON-TB Gold in-Tube (QFT) and T-SPOT. Read More

Carbohydr Polym 2018 Oct 7;197:403-413. Epub 2018 Jun 7.

Department of Light Chemical Engineering, Guangdong Polytechnic, Foshan 528041, PR China. Electronic address:

Lung-targeted genipin-crosslinked deacetylated chitosan (GEN-CS)/isoniazid (INH)/rifampin (RMP) nanogel particles (NGPs) were prepared as a treatment for tuberculosis caused by multidrug-resistant Mycobacterium tuberculosis (MTB) to surmount the undesirable side effects and decrease the cytotoxicity of INH and RMP when being against MTB. The size, morphology, in vitro release property, long-term antibacterial performance, stability, in vitro cytotoxicity, in vivo toxicity, and in vivo release property of GEN-CS/INH/RMP NGPs inhalation powder were investigated. The results showed that the GEN-CS/INH/RMP NGPs inhalation powder exhibited extended antibacterial activity because of its long-term release of INH and RMP. Read More

BMC Infect Dis 2018 07 11;18(1):317. Epub 2018 Jul 11.

University of St Andrews Medical School, St Andrews, UK.

Background: The incidence and severity of tuberculosis chemotherapy toxicity is poorly characterised. We used data available from patients in the REMoxTB trial to provide an assessment of the risks associated with the standard regimen and two experimental regimens containing moxifloxacin.

Methods: All grade 3 & 4 adverse events (AEs) and their relationship to treatment for patients who had taken at least one dose of therapy in the REMoxTB clinical trial were recorded. Read More

Am J Respir Crit Care Med 2018 09;198(5):657-666

9 Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts.

Rationale: We examined whether increased rifampin doses could shorten standard therapy for tuberculosis without increased toxicity.

Objectives: To assess the differences across three daily oral doses of rifampin in change in elimination rate of Mycobacterium tuberculosis in sputum and frequency of rifampin-related adverse events.

Methods: We conducted a blinded, randomized, controlled phase 2 clinical trial of 180 adults with new smear-positive pulmonary tuberculosis, susceptible to isoniazid and rifampin. Read More

J Diet Suppl 2018 Jun 28:1-14. Epub 2018 Jun 28.

a Department of Zoology , Panjab University , Chandigarh , India.

First-line antituberculosis drugs, namely, isoniazid (INH), rifampicin (RIF), and pyrazinamide (PZA), contribute to diverse pathological complications. Testicular toxicity is one such complication. Berberis aristata DC is an herb with potentially curative characteristics. Read More

Pharm Nanotechnol 2018 ;6(3):209-217

School of Pharmacy, BBD University, Lucknow (UP), India.

Background: Tuberculosis (TB) is one of the major health challenge in the world. The current treatment of TB needs daily administration of combined drug therapy for six or more months. Sometime non-adherence and less bioavailability from current therapy develops multidrug resistance, as a result, high dose requirement and subsequent intolerable toxicity are seen. Read More

Toxicol Lett 2018 Oct 21;295:256-269. Epub 2018 Jun 21.

Center for Molecular Metabolism, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, 200 Xiao Ling Wei Street, Nanjing 210094, PR China. Electronic address:

Isoniazid (INH) is a well-known therapeutic and preventive agent against tuberculosis. However, high rates of side effects with various symptoms concerning hepatotoxicity and neurotoxicity have been reported, hindering its wide and safe application in clinic. In this investigation, rats were intoxicated with INH by gavage at doses of 200 and 400 mg/kg for 7 consecutive days to develop a rat model of acute INH-induced toxicity, which was investigated by a H NMR-based metabolomics complemented with clinical assays, histopathological inspection and western blotting. Read More

Respirology 2018 10 14;23(10):893-900. Epub 2018 Jun 14.

Denver Health and Hospital Authority, Denver Public Health Department, CO, USA.

Diagnosing and treating latent tuberculosis (TB) infection (LTBI) is recognized by the World Health Organization as an important strategy to accelerate the decline in global TB and achieve TB elimination. Even among low-TB burden countries that have achieved high rates of detection and successful treatment for active TB, a number of barriers have prevented implementing or expanding LTBI treatment programmes. Of those infected with TB, relatively few will develop active disease and the current diagnostic tests have a low predictive value. Read More

Environ Toxicol Pharmacol 2018 Jul 15;61:87-94. Epub 2018 May 15.

Addiriyah Chair for Environmental Studies, College of Science, King Saud University, P.O Box 2455, Riyadh 11451, Saudi Arabia. Electronic address:

The Drug-induced liver injury is one of the common unfavourable impacts, which seriously affects any drug therapy. This study documented the hepatoprotective efficacy of lawsone, the major bioactive naphthoquinone present in Lawsonia inermis L. (Lythraceae) using in vitro and in vivo models. Read More

J Integr Med 2018 07 8;16(4):263-272. Epub 2018 May 8.

Histopathology Laboratory, Braithwaite Memorial Specialist Hospital, 50001 Rivers State, Nigeria; Medical Laboratory Science Department, Faculty of Science, Rivers State University of Science and Technology, Nkpoku Oroworukwo, Port Harcourt, PMB 5080 Rivers State, Nigeria.

Objectives: The aim of this study is to evaluate the hepatoprotective effect of Lasianthera africana (Icacinaceae) against isoniazid (INH) and rifampicin (RIF)-induced liver damage in rats.

Methods: The hepatoprotective effects of hot aqueous L. africana (HALA) leaf extract (0. Read More

Toxicol In Vitro 2018 Sep 8;51:83-94. Epub 2018 May 8.

Department of Chemical Engineering, Virginia Tech, Suite 245 Goodwin Hall, 635 Prices Fork Road, Blacksburg, VA 24061, USA; ICTAS Center for Systems Biology of Engineered Tissue, Virginia Tech, 333 Kelly Hall, 325 Stanger Street, Blacksburg, VA 24061, USA; School of Biomedical Engineering and Sciences, Virginia Tech, 333 Kelly Hall, 325 Stanger Street, Blacksburg, VA 24061, USA. Electronic address:

High-throughput screening (HTS) of liver toxicants can bridge the gap in understanding adverse effects of chemicals on humans. Toxicity testing of mixtures is time consuming and expensive, since the number of possible combinations increases exponentially with the number of chemicals. The combination of organotypic culture models (OCMs) and HTS assays can lead to the rapidly evaluation of chemical toxicity in a cost and time-effective manner while prioritizing chemicals that warrant additional investigation. Read More

Pharmacogn Mag 2018 Apr-Jun;14(54):180-185. Epub 2018 Apr 10.

Department of Pharmacology, Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh, India.

Background: Medicinal herbs are significantly effective against a variety of liver disorders and was traditionally used for the treatment of anti-inflammatory, pain disorder, and various types of hepatic ailment.

Objective: The purpose of this study was to evaluate the hepatoprotective activity of fruit peel extract against antitubercular drugs (isoniazid + rifampicin [INH + RIF])-induced hepatotoxicity in rats.

Materials And Methods: Liver toxicity was induced by INH + RIF at a dose level of 50 mg/kg each, intraperitoneally. Read More

J Control Release 2018 06 19;279:234-242. Epub 2018 Apr 19.

Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address:

Prostate cancer (PCa) is the most frequent malignant cancer among men in the USA, leading to substantial morbidity and mortality, while the existing treatments have restricted therapeutic benefits for patients with hormone-refractory PCa (HRPC) and metastatic PCa. Recent studies show that advanced PCa exhibits an increase in the expression of monoamine oxidase A (MAOA) which is a mitochondria enzyme, and MAOA activity inhibition could restrict metastasis and extend mice survival in PCa xenografts. These findings suggest MAOA can be a potential target to treat PCa. Read More

S Afr Med J 2018 Mar 28;108(4):271-274. Epub 2018 Mar 28.

Division of Neurology, Groote Schuur Hospital and Faculty of Health Sciences, University of Cape Town, South Africa.

A high proportion of HIV-positive patients in South Africa receive concomitant efavirenz (EFV) and isoniazid (INH) therapy. EFV is metabolised in the liver via CYP2B6, and genetic polymorphism of CYP2B6 is known to result in slowed metabolism of the drug. INH is also metabolised in the liver, causing inhibition of a pathway that plays an important role in slow EFV metabolisers. Read More

Molecules 2018 Apr 4;23(4). Epub 2018 Apr 4.

Institute of Pharmacy, Martin-Luther-University Halle-Wittenberg, 06120 Halle, Germany.

The number of effective first-line antibiotics for the treatment of infection is strongly limited to a few drugs. Due to emerging resistance against those drugs, second- and third-line antibiotics have been established in therapy with certain problems and also increasing mycobacterial resistance. An alternative to such novel drugs or combined therapeutic regimes which may reduce resistance development is finding enhancers of mycobacterial drug effectiveness, especially enhancers that counteract causative resistance mechanisms. Read More

Eur J Med Chem 2018 Apr 20;150:864-875. Epub 2018 Mar 20.

Centre for Nano and Material Sciences, Jain University, Jain Global Campus, Jakkasandra Post, Bangalore, 562112, India. Electronic address:

As a contribution to the development of novel coumarin-oxime ether conjugates with therapeutically interesting properties, a series of coumarin-oxime ether (1a-1j) was synthesised using S2 reaction of bromomethyl coumarins with butane-2,3-dione monoxime. Invitro anti-tuberculosis activityagainstMTBHRv strain was established for the coumarin-oxime ether (1a-1j). Most of the compounds exhibited significant activity with minimum inhibitory concentration (MIC)in the range of 0. Read More

BMC Med 2018 03 28;16(1):46. Epub 2018 Mar 28.

University of St Andrews Medical School, St Andrews, UK.

Background: Drug-induced liver injury (DILI) is a common complication of tuberculosis treatment. We utilised data from the REMoxTB clinical trial to describe the incidence of predisposing factors and the natural history in patients with liver enzyme levels elevated in response to tuberculosis treatment.

Methods: Patients received either standard tuberculosis treatment (2EHRZ/4HR), or a 4-month regimen in which moxifloxacin replaced either ethambutol (isoniazid arm, 2MHRZ/2MHR) or isoniazid (ethambutol arm, 2EMRZ/2MR). Read More

Front Pharmacol 2018 7;9:198. Epub 2018 Mar 7.

Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, China.

Tuberculosis (TB) is one of the oldest infectious diseases that affected humankind and remains one of the world's deadliest communicable diseases that could be considered as global emergency, but the discovery and development of isoniazid (INH) in the 1950s paved the way to an effective single and/or combined first-line anti-TB therapy. However, administration of INH induces severe hepatic toxicity in some patients. Previously, we establish a rat model of INH hepatotoxicity utilizing the inflammatory stress theory, in which bacterial lipopolysaccharide (LPS) potentially enhanced INH toxicity. Read More

Bioorg Med Chem Lett 2018 05 8;28(8):1309-1312. Epub 2018 Mar 8.

Department of Chemistry, Guru Nanak Dev University, Amritsar 143005, India. Electronic address:

The success in exploring anti-tubercular potency of nitroimidazole and quinoline, the core moieties of recently approved anti-tubercular drugs instigated us to synthesize a series of alkylated/aminated 2-methyl-5-nitroimidazoles and nitroimidazole-7-chloroquinoline conjugates and to evaluate them for their activities against Mycobacterium tuberculosis as well as for their cytotoxicity towards the J774 murine macrophage cell line. Although the synthesized compounds did not surpass the activity of the standard drug Isoniazid, they have appreciable activities with minimal cytotoxicity. The synthesized nitroimidazole-7-chloroquinoline conjugate, 11c, having butyl chain as linker, proved to be the most potent among the series with an MIC value of 2. Read More

NPJ Syst Biol Appl 2018 26;4:10. Epub 2018 Feb 26.

Institute of Applied Microbiology-iAMB, Aachen Biology and Biotechnology-ABBt, RWTH Aachen University, 52074 Aachen, Germany.

Drug-induced perturbations of the endogenous metabolic network are a potential root cause of cellular toxicity. A mechanistic understanding of such unwanted side effects during drug therapy is therefore vital for patient safety. The comprehensive assessment of such drug-induced injuries requires the simultaneous consideration of both drug exposure at the whole-body and resulting biochemical responses at the cellular level. Read More

Life Sci 2018 Apr 27;199:23-33. Epub 2018 Feb 27.

PCS 103 Genotoxicity Lab, Division of Toxicology and Experimental Medicine, CSIR-Central Drug Research Institute, B.S. 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India. Electronic address:

Aims: Long-term treatment of Isoniazid (INH) in tuberculosis (TB) patients can lead to anti-tuberculosis drug-induced hepatotoxicity. To understand the mechanism of hepatotoxicity, an attempt has been made to elucidate the role of Nrf2, a transcription factor induced by oxidative stress, in INH induced apoptosis liver cancer cell lines.

Materials And Methods: Cytotoxicity was evaluated by MTT assay. Read More

Eur J Med Chem 2018 Feb 31;146:529-540. Epub 2018 Jan 31.

Fundacao Oswaldo Cruz, Instituto de Tecnologia em Fármacos, Farmanguinhos-Fiocruz, Departamento de Sintese Farmacos, Manguinhos, 21041-250 Rio de Janeiro, RJ, Brazil. Electronic address:

Tuberculosis (TB) is one of the leading causes of death worldwide. The emergence of multi-drug resistant strains of Mycobacterium tuberculosis (Mtb) and TB-HIV co-infection are major public health challenges. The anti-TB drugs of first choice were developed more than 4 decades ago and present several adverse effects, making the treatment of TB even more complicated and the development of new chemotherapeutics for this disease imperative. Read More

Arch Argent Pediatr 2018 Feb;116(1):e115-e120

Unidad de Toxicología, Hospital de Niños "Ricardo Gutiérrez", Ciudad Autónoma de Buenos Aires.

Serotonin toxicity is a potentially life-threatening condition associated with increased serotonergic activity in the central nervous system. It is seen with therapeutic medication use, intentional self-poisoning and inadvertent interactions (SSRI-isoniazid). Although this pathology is increasingly common, it is not well recognized by physicians and manifestations may be wrongly attributed to another cause. Read More

J Tradit Complement Med 2018 Jan 21;8(1):239-243. Epub 2017 Jun 21.

Zoonoses Research Center, Jahrom University of Medical Sciences, Jahrom, Iran.

Introduction: Isoniazid is a drug for treatment of tuberculosis. One of the main side effects of this drug is hepatotoxicity, which is a major cause of treatment interruption in tuberculosis. This study is about the preventive effect of Salep on this side effect of isoniazid. Read More

J Acquir Immune Defic Syndr 2018 04;77(4):405-412

Section of Infectious Diseases, Boston Medical Center, Boston, MA.

Background: Isoniazid preventive therapy (IPT) reduces mortality among people living with HIV (PLHIV) and is recommended for those without active tuberculosis (TB) symptoms. Heavy alcohol use, however, is contraindicated for liver toxicity concerns. We evaluated the risks and benefits of IPT at antiretroviral therapy (ART) initiation to ART alone for PLHIV who are heavy drinkers in 3 high TB-/HIV-burden countries. Read More

Eur J Pharm Sci 2018 Mar 8;114:103-113. Epub 2017 Dec 8.

CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra 1317, 4585-116 Gandra, Portugal.

Mannose receptor is highly expressed on alveolar macrophages, being a potential target to promote the specific local drug delivery of anti-tuberculosis agents through the use of functionalized nanocarriers. In this work, isoniazid (Isn)-loaded solid lipid nanoparticles (SLN), reinforced with stearylamine (SA) were produced by double emulsion technique and further surface-functionalized with mannose in a straightforward chemical approach. Upon pre-formulation assessment, SLN close to 500 nm average size, positively charged and with association efficiency of ISN close to 50% were obtained. Read More

Expert Opin Drug Metab Toxicol 2018 Jan 18;14(1):59-82. Epub 2017 Dec 18.

a Unit of Infectious Diseases, Department of Medical Sciences , University of Torino , Torino , Italy.

Introduction: WHO global strategy is to end tuberculosis epidemic by 2035. Pharmacokinetic and pharmacogenetic studies are increasingly performed and might confirm their potential role in optimizing treatment outcome in specific settings and populations. Insufficient drug exposure seems to be a relevant factor in tuberculosis outcome and for the risk of phenotypic resistance. Read More

Molecules 2017 Nov 30;22(12). Epub 2017 Nov 30.

Department of Biological Sciences, Cork Institute of Technology, Bishopstown, Cork T12 P928, UK.

Novel 1-(2-{3-/4-[(alkoxycarbonyl)amino]phenyl}-2-hydroxyethyl)-4-(2-fluorophenyl)-piperazin-1-ium chlorides (alkoxy = methoxy to butoxy; -) have been designed and synthesized through multistep reactions as a part of on-going research programme focused on finding new antimycobacterials. Lipophilic properties of these compounds were estimated by RP-HPLC using methanol/water mobile phases with a various volume fraction of the organic modifier. The log values, which were extrapolated from intercepts of a linear relationship between the logarithm of a retention factor (log ) and volume fraction of a mobile phase modifier (), varied from 2. Read More