scholarly journals Synthesis, Characterization, and Biological Evaluation of New Derivatives Targeting MbtI as Antitubercular Agents

2021 ◽  
Vol 14 (2) ◽  
pp. 155 ◽  
Author(s):  
Matteo Mori ◽  
Giovanni Stelitano ◽  
Laurent R. Chiarelli ◽  
Giulia Cazzaniga ◽  
Arianna Gelain ◽  
...  
Keyword(s):  
Phenyl Ring ◽  
Antitubercular Activity ◽  
Biological Evaluation ◽  
Antitubercular Agents ◽  
Structural Requirements ◽  
Future Studies ◽  
Structure Activity ◽  
Salicylate Synthase ◽  
Essential Enzyme ◽  
New Compounds

Tuberculosis (TB) causes millions of deaths every year, ranking as one of the most dangerous infectious diseases worldwide. Because several pathogenic strains of Mycobacterium tuberculosis (Mtb) have developed resistance against most of the established anti-TB drugs, new therapeutic options are urgently needed. An attractive target for the development of new antitubercular agents is the salicylate synthase MbtI, an essential enzyme for the mycobacterial siderophore biochemical machinery, absent in human cells. A set of analogues of I and II, two of the most potent MbtI inhibitors identified to date, was synthesized, characterized, and tested to elucidate the structural requirements for achieving an efficient MbtI inhibition and a potent antitubercular activity with this class of compounds. The structure-activity relationships (SAR) here discussed evidenced the importance of the furan as part of the pharmacophore and led to the preparation of six new compounds (IV–IX), which gave us the opportunity to examine a hitherto unexplored position of the phenyl ring. Among them emerged 5-(3-cyano-5-(trifluoromethyl)phenyl)furan-2-carboxylic acid (IV), endowed with comparable inhibitory properties to the previous leads, but a better antitubercular activity, which is a key issue in MbtI inhibitor research. Therefore, compound IV offers promising prospects for future studies on the development of novel agents against mycobacterial infections.

Novel Benzylidenehydrazide-1,2,3-Triazole Conjugates as Antitubercular Agents: Synthesis and Molecular Docking

2019 ◽  
Vol 19 (14) ◽  
pp. 1178-1194 ◽  
Author(s):  
Mubarak H. Shaikh ◽  
Dnyaneshwar D. Subhedar ◽  
Laxman Nawale ◽  
Dhiman Sarkar ◽  
Firoz A. Kalam Khan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antitubercular Activity ◽  
Docking Study ◽  
Antitubercular Agents ◽  
Molecular Docking Study ◽  
Activity Data ◽  
Structure Activity ◽  
Starting Point ◽  
Adme Properties

Background & Objectives:Novel 1,2,3-triazole based benzylidenehydrazide derivatives were synthesized and evaluated for antitubercular activity against Mycobacterium tuberculosis (MTB) H37Ra, M. bovis BCG and cytotoxic activity. Most of the derivatives exhibited promising in vitro potency against MTB characterized by lower MIC values.Methods:Among all the synthesized derivatives, compound 6a and 6j were the most active against active and dormant MTB H37Ra, respectively. Compound 6d was significantly active against dormant and active M. bovis BCG.Results:The structure activity relationship has been explored on the basis of anti-tubercular activity data. The active compounds were also tested against THP-1, A549 and Panc-1 cell lines and showed no significant cytotoxicity. Further, the synthesized compounds were found to have potential antioxidant with IC50 range = 11.19-56.64 µg/mL. The molecular docking study of synthesized compounds was performed against DprE1 enzyme of MTB to understand the binding interactions.Conclusion:Furthermore, synthesized compounds were also analysed for ADME properties and the potency of compounds indicated that, this series can be considered as a starting point for the developement of novel and more potent anti-tubercular agents in future.

scholarly journals New insight into structure-activity of furan-based salicylate synthase (MbtI) inhibitors as potential antitubercular agents

2019 ◽  
Vol 34 (1) ◽  
pp. 823-828 ◽  
Author(s):  
Laurent R. Chiarelli ◽  
Matteo Mori ◽  
Giangiacomo Beretta ◽  
Arianna Gelain ◽  
Elena Pini ◽  
...  
Keyword(s):  
Antitubercular Agents ◽  
Structure Activity ◽  
Salicylate Synthase ◽  
Insight Into

scholarly journals Synthesis and evaluation of β-hydroxytriazoles and related compounds as antitubercular agents

2015 ◽  
Vol 3 (1) ◽  
pp. 82-96 ◽  
Author(s):  
Christophe Menendez ◽  
Giorgia Mori ◽  
Mathilde Maillot ◽  
Isabelle Fabing ◽  
Chantal Carayon ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Antitubercular Activity ◽  
Propargyl Bromide ◽  
Antitubercular Agents ◽  
Oxidation Reactions ◽  
Mycobacterium Tuberculosis H37rv ◽  
Barbier Reaction ◽  
New Compounds ◽  
Related Compounds

A new series of β-hydroxytriazoles were synthesized and evaluated as Mycobacterium tuberculosis inhibitors. Our strategy implied the synthesis of alkyne precursors through a Barbier reaction between benzaldehydes and propargyl bromide followed by click chemistry to afford substituted β-hydroxyl benzyltriazoles. These compounds are also key intermediates either for oxidation reactions leading to α,β-diketotriazoles or for elimination reactions affording styryl triazoles. Evaluation of all new compounds for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv resulted in compounds with MIC up to 7 μM.

Novel 2-(2-phenalkyl)-1H-benzo[d]imidazoles as antitubercular agents. Synthesis, biological evaluation and structure–activity relationship

2015 ◽  
Vol 23 (9) ◽  
pp. 2112-2120 ◽  
Author(s):  
Katarzyna Gobis ◽  
Henryk Foks ◽  
Karolina Suchan ◽  
Ewa Augustynowicz-Kopeć ◽  
Agnieszka Napiórkowska ◽  
...  
Keyword(s):  
Structure Activity Relationship ◽  
Biological Evaluation ◽  
Activity Relationship ◽  
Antitubercular Agents ◽  
Structure Activity

scholarly journals Design, Synthesis and Biological Evaluation of N-((2-phenyloxazol-4-yl)methyl) Pyrimidine Carboxamide Derivatives as Potential Fungicidal Agents

2020 ◽  
Vol 26 (1) ◽  
pp. 185-191
Author(s):  
Danling Huang ◽  
Shumin Zheng ◽  
Yong-Xian Cheng
Keyword(s):  
Sclerotinia Sclerotiorum ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
H Nmr ◽  
Structure Activity ◽  
Colletotrichum Fragariae ◽  
New Compounds ◽  
Synthesis And Biological Evaluation ◽  
Commercial Fungicide ◽  
C Nmr

Abstract Twelve N-((2-phenyloxazol-4-yl)methyl) pyrimidine carboxamide derivatives were designed, synthesized, and characterized by 1H NMR, 13C NMR, and HRMS. The fungicidal activities of these new compounds against Sclerotinia sclerotiorum, Botrytis cinereal, and Colletotrichum fragariae were evaluated. The results indicated that compounds 5b, 5f, and 5g displayed potential fungicidal activities against tested fungi, especially 5f exhibited IC50 value of 28.9 mg/L against S. sclerotiorum. Moreover, the compounds 5f and 5g showed IC50 values of 54.8 mg/L and 62.2 mg/L against C. fragariae respectively, which shows that they were more active than the commercial fungicide hymexazol. The superficial structure-activity relationships were discussed, which may be of benefit for the development of fungicides and discovery of novel fungicides.

Strategically Placed Trifluoromethyl Substituent in the Realm of Antitubercular Drug Design

2019 ◽  
Vol 14 (2) ◽  
pp. 114-123 ◽  
Author(s):  
Sidhartha S. Kar ◽  
Cinu A. Thomas
Keyword(s):  
Drug Design ◽  
Phenyl Ring ◽  
Antitubercular Activity ◽  
Trifluoromethyl Group ◽  
Antitubercular Agents ◽  
Antitubercular Drug ◽  
Pharmacokinetic Properties ◽  
Prime Objective ◽  
Electron Withdrawing Group

Background:Fluorinated substituents have played, and continue to play an important role in antitubercular drug design. Nonetheless, previous works have indicated that organofluorines like –F, CF3, -OCF3, and CHF2 etc have been used to modulate the pharmacodynamic and pharmacokinetic behaviour of antitubercular agents. Among the fluorinated groups, trifluoromethyl (-CF3) substituent is a very familiar pharmacophore used widely in antitubercular research.Objective:This review assesses the development of selected trifluoromethyl group bearing antitubercular agents that are either in treatment or considered to be potential. The prime objective of the present investigation was to provide initial evidences for the hypothesis that addition of trifluoromethyl group to antiTB agents could improve their potency. We also aimed to contribute to a better understanding of the role of trifluoromethyl group on drug-likeness antitubercular activity.Methods:In this review, we first brief out the possible effect of –CF3 substituent on pharmacodynamic and pharmacokinetic properties of drugs. Next, we turn to emphasize on the effect of trifluoromethyl substituent on different antitubercular scaffolds. Finally, we open the topic for the researchers to design potential antitubercular agents suitably substituted with fluorinated groups.Results:This review suggests that the replacement of –CF3 group in heterocyclic as well as phenyl ring led to the improvement in pharmacodynamic and pharmacokinetic properties of the compounds. Hence it's not surprising to see –CF3 group emerging as an alternative electron withdrawing group instead of halogens in many promising antitubercular agents.Conclusion:This unusual spectrum of advantage allied with its lipophilicity enhancing effect, made –CF3 group distinct from other substituents in modern antitubercular drug design. The present study provides conceptual advances to the understanding of the physicochemical properties of –CF3 group and its effect on antitubercular activity.

scholarly journals Neuroprotective Norsesquiterpenoids and Triterpenoids from Populus euphratica Resins

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4379 ◽  
Author(s):  
Yun-Yun Liu ◽  
Dan-Ling Huang ◽  
Yun Dong ◽  
Da-Peng Qin ◽  
Yong-Ming Yan ◽  
...  
Keyword(s):  
Computational Methods ◽  
Cell Injury ◽  
Populus Euphratica ◽  
Biological Evaluation ◽  
Neural Cell ◽  
Activity Relationship ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Structure Activity ◽  
New Compounds

Two new octanorlanostane-type triterpenes, euphraticanoids A and B (1 and 2), two new trinorsesquiterpenoids, euphraticanoids C and D (3 and 4), and eight known triterpenoids (5, 6, 8–13) along with one steroid (7) were isolated from Populus euphratica resins. The structures of these new compounds, including their absolute configurations, were characterized by spectrocsopic, chemical, and computational methods. Biological evaluation revealed that compounds 4, 7–9, 12, and 13 display neuroprotective activities in H2O2-induced HT-22 cells with 4, 8, and 9 occurring in a concentration-dependent manner and 7, 12, and 13 reaching the maximum effects at 20 μM. Meanwhile, the neuroprotective properties of all isolates were accessed using glutamate-induced SH-SY5Y cells and disclosed that compounds 3, 4, 8, and 9 could dose-dependently protect neural cell injury in a concentration range of 10–40 μM. Finally, a brief structure–activity relationship was briefly discussed.

scholarly journals Quinazolinone novel derivatives synthesis and their Biological Evaluation as Antimicrobial and Antitubercular agents

2019 ◽  
Vol 10 (4) ◽  
pp. 3026-3034 ◽  
Author(s):  
Neha Krishnarth ◽  
Santosh Kumar Verma ◽  
Anurag
Keyword(s):  
Antimicrobial Activity ◽  
Antitubercular Activity ◽  
Biological Evaluation ◽  
Maximum Activity ◽  
Effective Vaccine ◽  
Antitubercular Agents ◽  
Global Level ◽  
Major Health ◽  
Increased Risk ◽  
Quinazolinone Derivatives

At a global level, tuberculosis (TB) is the disease of human values. It suffers from major health, social and economic burden in many countries. There is an inability of an effective vaccine or the use of vaccine were too long and expensive, have increased risk of spread of this disease.  A  series of quinazolinone derivatives prepared with the help of 2-Amino-3,4,5-trimethoxy benzoic acid and Vilsmeir reagent.  Synthesized  compounds  were  characterized  by  various  spectral  methods.  Different activity like antimicrobial activity of the synthesised compounds were performed,  and the most active compounds of the series were further screened for antitubercular activity against bacteria mycobacterium  H37Rv.  Results  showed that all the synthesized compounds have antimicrobial activity. Compounds  IV c,  IV f, IV h  and IV o showed maximum activity in the synthesized series.  These four compounds further screened for antitubercular activity.  Compounds  IV c,  IV f, IV h  and  IV o showed significant antitubercular activity.

Synthesis of 2-Hydroxynaphthyl Pyrazolines Containing Isoniazid Moiety: A Potential Antitubercular Agents

2021 ◽  
Vol 18 ◽  
Author(s):  
Gajanan Kottapalle ◽  
Nagesh Deshmukh ◽  
Avinash Shinde
Keyword(s):  
Phenyl Ring ◽  
Antitubercular Activity ◽  
Moderate Activity ◽  
Alamar Blue ◽  
Antitubercular Agents ◽  
Tuberculosis Strain ◽  
Halogen Compound ◽  
Electron Withdrawing Group ◽  
Strain H37rv ◽  
Mycobacterium Tuberculosis Strain

: The new series of pyrazolines derivatives containing isoniazid moiety were synthesized from 2-hydroxynaphthyl functionalized chalcones and isoniazid using sodium hydroxide as a base in 2-ethoxy ethanol.We are evaluated for their antitubercular activity against Mycobacterium tuberculosis strain (H37Rv) by Microplate Alamar Blue Assay (MABA) some of the tested compounds 3a, 3b, and 3c, were found to have higher antitubercular activity than the selected standard drugs, where as the compounds 3d, 3e, 3i and 3j found to have higher antitubercular activity than Streptomycin and same as that of drug Pyrazinamide and Ciprofloxacin. While remaining compound showed moderate activity. Where as it is found that the disubstituted halogen compound and electron withdrawing group on the phenyl ring are important substitution for increase in antitubercular activity.

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