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Luke C Henderson - One of the best experts on this subject based on the ideXlab platform.
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novel 1 4 substituted 1 2 3 triazoles as Antitubercular agents
ChemMedChem, 2015Co-Authors: Jarrad M Altimari, Samantha C Hockey, Helena I Boshoff, Andaleeb Sajid, Luke C HendersonAbstract:Tuberculosis (TB) remains a pressing unmet medical need, particularly with the emergence of multidrug-resistant and extensively drug-resistant tuberculosis. Here, a series of 1,4-substituted-1,2,3-triazoles have been synthesized and evaluated as potential Antitubercular agents. These compounds were assembled via click chemistry in high crude purity and in moderate to high yield. Of the compounds tested, 12 compounds showed promising Antitubercular activity with six possessing minimum inhibitory concentration (MIC) values <10 μg mL(-1) , and total selectivity for Mycobacterium tuberculosis (Mtb) growth inhibition. A second set of 21 compounds bearing variations on ring C were synthesized and evaluated. This second library gave an additional six compounds displaying MIC values ≤10 μg mL(-1) and total selectivity for Mtb growth inhibition. These compounds serve as an excellent starting point for further development of Antitubercular therapies.
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Novel 1,4‐Substituted‐1,2,3‐Triazoles as Antitubercular Agents
ChemMedChem, 2015Co-Authors: Jarrad M Altimari, Samantha C Hockey, Helena I Boshoff, Andaleeb Sajid, Luke C HendersonAbstract:Tuberculosis (TB) remains a pressing unmet medical need, particularly with the emergence of multidrug-resistant and extensively drug-resistant tuberculosis. Here, a series of 1,4-substituted-1,2,3-triazoles have been synthesized and evaluated as potential Antitubercular agents. These compounds were assembled via click chemistry in high crude purity and in moderate to high yield. Of the compounds tested, 12 compounds showed promising Antitubercular activity with six possessing minimum inhibitory concentration (MIC) values
Kishan P. Haval - One of the best experts on this subject based on the ideXlab platform.
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Design and synthesis of new indanol-1,2,3-triazole derivatives as potent Antitubercular and antimicrobial agents.
Bioorganic & medicinal chemistry letters, 2020Co-Authors: Pramod S. Phatak, Vagolu Siva Krishna, Dharmarajan Sriram, Rajubai D. Bakale, Sambhaji T. Dhumal, Ravibhushan S. Kulkarni, Prashant P. Dixit, Vijay M. Khedkar, Kishan P. HavalAbstract:Abstract In a search of new Antitubercular agents, herein we have reported a series of new thirty-two indanol-1,2,3-triazole derivatives. The synthesized compounds were screened for their in vitro Antitubercular and antimicrobial activities. Among the screened compounds, most of the compounds have displayed good Antitubercular activity against Mycobacterium tuberculosis H37Rv. The compound 5g has been identified as potent Antitubercular agent with MIC value 1.56 µM. The most active compounds of the series were further studied for their cytotoxicity against HEK 293 cells using MTT assay and found to be nontoxic. In addition, ten compounds were shown good antimicrobial activities against both antibacterial and antifungal pathogens. A molecular docking study against Mycobacterial enoyl-ACP-reductase (InhA) was performed to gain an insight into the molecular mechanism of Antitubercular action. The pharmacokinetic parameters of these compounds were studied and displayed acceptable drug-likeness score.
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Novel isoniazid embedded triazole derivatives: synthesis, Antitubercular and antimicrobial activity evaluation
Bioorganic & medicinal chemistry letters, 2020Co-Authors: Pravin S. Patil, Dharmarajan Sriram, Prashant P. Dixit, Vijay M. Khedkar, Sanghratna L. Kasare, Nitin B. Haval, Estharla Madhu Rekha, Kishan P. HavalAbstract:Abstract In the present study, a series of sixteen new isoniazid embedded triazole derivatives have been synthesized. These compounds were evaluated for their in vitro Antitubercular and antimicrobial activities. Among the screened compounds, six have exhibited potent Antitubercular activity against Mycobacterium tuberculosis H37Rv strain with MIC value 0.78 μg/mL, Whereas, three compounds have displayed activity with MIC value ranging from 1.56 to 3.125 μg/mL. The cytotoxicity of the active compounds was studied against RAW 264.7 cell line by MTT assay and no toxicity was observed even at 25 μg/mL concentration. The five compounds have displayed good antimicrobial activities. Molecular docking have been performed against mycobacterial InhA enzyme to gain an insight into the plausible mechanism of action which could pave the way for our endeavor to identify potent Antitubercular candidates. We believe that further optimization of these molecules may lead to potent Antitubercular agents.
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Synthesis, Antitubercular evaluation and molecular docking studies of phthalimide bearing 1,2,3-triazoles
2019Co-Authors: Pramod S. Phatak, Vagolu Siva Krishna, Dharmarajan Sriram, Rajubai D. Bakale, Sambhaji T. Dhumal, Lalita K. Dahiwade, Prafulla B. Choudhari, Kishan P. HavalAbstract:In a search for safer and potent Antitubercular agents, here a library of newly substituted dioxoisoindolinylmethyl-triazolyl-N-phenylacetamide derivatives (5a–l) has been synthesized via click chemistry approach. All synthesized compounds were evaluated for their Antitubercular activity against Mycobacterium tuberculosis H37Rv (MTB). Among the screened compounds, 5d, 5e, 5h, and 5l showed good Antitubercular activity. The compounds 5d and 5l have shown very effective Antitubercular activity against Mycobacterium tuberculosis H37Rv (MTB) with MIC 12.5 μg/mL. All the newly synthesized compounds were thoroughly characterized by 1H NMR, 13C NMR, and HRMS spectral data. We further performed exploratory docking studies on the crystal structure of Mycobacterium tuberculosis enoyl reductase to demonstrate the mechanism of Antitubercular activity.
Dharmarajan Sriram - One of the best experts on this subject based on the ideXlab platform.
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Design and synthesis of new indanol-1,2,3-triazole derivatives as potent Antitubercular and antimicrobial agents.
Bioorganic & medicinal chemistry letters, 2020Co-Authors: Pramod S. Phatak, Vagolu Siva Krishna, Dharmarajan Sriram, Rajubai D. Bakale, Sambhaji T. Dhumal, Ravibhushan S. Kulkarni, Prashant P. Dixit, Vijay M. Khedkar, Kishan P. HavalAbstract:Abstract In a search of new Antitubercular agents, herein we have reported a series of new thirty-two indanol-1,2,3-triazole derivatives. The synthesized compounds were screened for their in vitro Antitubercular and antimicrobial activities. Among the screened compounds, most of the compounds have displayed good Antitubercular activity against Mycobacterium tuberculosis H37Rv. The compound 5g has been identified as potent Antitubercular agent with MIC value 1.56 µM. The most active compounds of the series were further studied for their cytotoxicity against HEK 293 cells using MTT assay and found to be nontoxic. In addition, ten compounds were shown good antimicrobial activities against both antibacterial and antifungal pathogens. A molecular docking study against Mycobacterial enoyl-ACP-reductase (InhA) was performed to gain an insight into the molecular mechanism of Antitubercular action. The pharmacokinetic parameters of these compounds were studied and displayed acceptable drug-likeness score.
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Novel isoniazid embedded triazole derivatives: synthesis, Antitubercular and antimicrobial activity evaluation
Bioorganic & medicinal chemistry letters, 2020Co-Authors: Pravin S. Patil, Dharmarajan Sriram, Prashant P. Dixit, Vijay M. Khedkar, Sanghratna L. Kasare, Nitin B. Haval, Estharla Madhu Rekha, Kishan P. HavalAbstract:Abstract In the present study, a series of sixteen new isoniazid embedded triazole derivatives have been synthesized. These compounds were evaluated for their in vitro Antitubercular and antimicrobial activities. Among the screened compounds, six have exhibited potent Antitubercular activity against Mycobacterium tuberculosis H37Rv strain with MIC value 0.78 μg/mL, Whereas, three compounds have displayed activity with MIC value ranging from 1.56 to 3.125 μg/mL. The cytotoxicity of the active compounds was studied against RAW 264.7 cell line by MTT assay and no toxicity was observed even at 25 μg/mL concentration. The five compounds have displayed good antimicrobial activities. Molecular docking have been performed against mycobacterial InhA enzyme to gain an insight into the plausible mechanism of action which could pave the way for our endeavor to identify potent Antitubercular candidates. We believe that further optimization of these molecules may lead to potent Antitubercular agents.
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Novel 1,3,4-oxadiazoles as Antitubercular agents with limited activity against drug-resistant tuberculosis.
Future medicinal chemistry, 2019Co-Authors: Vitthal B. Makane, Vagolu Siva Krishna, Manjulika Shukla, B. Mahizhaveni, Sunil Misra, Sidharth Chopra, Dharmarajan Sriram, V.n. Azger Dusthackeer, Eruva Vamshi Krishna, Haridas B. RodeAbstract:In recent times, heterocyclic chemotypes are being explored for the development of new antimycobacterials that target the drug-resistant tuberculosis. Here, we are disclosing the 5-substitued 2-mercapto-1,3,4-oxadiazoles as potent Antitubercular agents. A small library of 2-mercapto-1,3,4-oxadiazoles was synthesized using various acids. The compounds were evaluated for antituberculosis activity against M. tuberculosis H37Rv. Compound 8j was identified as Antitubercular lead with MIC of 0.6 μg/ml against M. tuberculosis H37Rv. This compound was nontoxic to CHO-K1 cells and showed selectivity index of 39. Of note, 8j showed Antitubercular activity against pre-extensively drug-resistant clinical isolate of Mycobacterium with MIC of 2 μg/ml. This study provides potent Antitubercular agent which can be further optimized to discover novel antibiotics.
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Synthesis and evaluation of α-aminoacyl amides as Antitubercular agents effective on drug resistant tuberculosis.
European journal of medicinal chemistry, 2019Co-Authors: Vitthal B. Makane, Vagolu Siva Krishna, E. Vamshi Krishna, Manjulika Shukla, B. Mahizhaveni, Sunil Misra, Sidharth Chopra, Dharmarajan Sriram, V.n. Azger Dusthackeer, Haridas B. RodeAbstract:Abstract The development of an effective Antitubercular agent is a challenge due to the complex nature of tuberculosis. Herein, we report the synthesis and evaluation of α-aminoacyl amides as Antitubercular agents. The systematic medicinal chemistry approach led to identification of optimal substitutions required for the activity. Compound 11l was identified as Antitubercular lead with drug like properties. Further, 11l selectively inhibited M. tuberculosis H37Rv with MIC value of 0.78 μM and was found to be non-toxic to CHO K1 cells. The lead compound inhibited multidrug resistant and Pre-Extensively drug resistant strains of Mycobacterium at 2 μg/mL and 8 μg/mL respectively.
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Synthesis, Antitubercular evaluation and molecular docking studies of phthalimide bearing 1,2,3-triazoles
2019Co-Authors: Pramod S. Phatak, Vagolu Siva Krishna, Dharmarajan Sriram, Rajubai D. Bakale, Sambhaji T. Dhumal, Lalita K. Dahiwade, Prafulla B. Choudhari, Kishan P. HavalAbstract:In a search for safer and potent Antitubercular agents, here a library of newly substituted dioxoisoindolinylmethyl-triazolyl-N-phenylacetamide derivatives (5a–l) has been synthesized via click chemistry approach. All synthesized compounds were evaluated for their Antitubercular activity against Mycobacterium tuberculosis H37Rv (MTB). Among the screened compounds, 5d, 5e, 5h, and 5l showed good Antitubercular activity. The compounds 5d and 5l have shown very effective Antitubercular activity against Mycobacterium tuberculosis H37Rv (MTB) with MIC 12.5 μg/mL. All the newly synthesized compounds were thoroughly characterized by 1H NMR, 13C NMR, and HRMS spectral data. We further performed exploratory docking studies on the crystal structure of Mycobacterium tuberculosis enoyl reductase to demonstrate the mechanism of Antitubercular activity.
Sudhir Sinha - One of the best experts on this subject based on the ideXlab platform.
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application of huisgen 3 2 cycloaddition reaction synthesis of 1 2 3 dihydrobenzofuran 2 yl methyl 1 2 3 triazoles and their Antitubercular evaluations
European Journal of Medicinal Chemistry, 2010Co-Authors: Rama P Tripathi, Amit Kumar Yadav, Arya Ajay, Surendra Singh Bisht, Vinita Chaturvedi, Sudhir SinhaAbstract:Abstract 1,4-Disubstituted-1,2,3-triazoles (3–27) have been synthesized by [3+2] cycloaddition of different 2-(azidomethyl)-dihydronaptho(benzo)furans (2a, 2b, 2c and 2d) with different alkynes. All the compounds were screened for Antitubercular activity against Mycobacterium tuberculosis H37Rv. Compounds 2a, 7, 9, 12 and 14 exhibited Antitubercular activities with MIC ranging from 12.5 to 3.12 μg/ml.
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A small library of trisubstituted pyrimidines as antimalarial and Antitubercular agents.
Bioorganic & medicinal chemistry letters, 2005Co-Authors: Anu Agarwal, Sudhir Sinha, Kumkum Srivastava, Sunil K. Puri, Prem M. S. ChauhanAbstract:Abstract A small library of 20 trisubstituted pyrimidines were synthesized and evaluated for their in vitro antimalarial and Antitubercular activities. Out of the total screened compounds, 16 compounds have shown in vitro antimalarial activity against Plasmodium falciparum in the range of 0.25–2 μg/mL and 8 compounds have shown Antitubercular activity against Mycobacterium tuberculosis H 37 Ra, at a concentration of 12.5 μg/mL.
Jarrad M Altimari - One of the best experts on this subject based on the ideXlab platform.
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novel 1 4 substituted 1 2 3 triazoles as Antitubercular agents
ChemMedChem, 2015Co-Authors: Jarrad M Altimari, Samantha C Hockey, Helena I Boshoff, Andaleeb Sajid, Luke C HendersonAbstract:Tuberculosis (TB) remains a pressing unmet medical need, particularly with the emergence of multidrug-resistant and extensively drug-resistant tuberculosis. Here, a series of 1,4-substituted-1,2,3-triazoles have been synthesized and evaluated as potential Antitubercular agents. These compounds were assembled via click chemistry in high crude purity and in moderate to high yield. Of the compounds tested, 12 compounds showed promising Antitubercular activity with six possessing minimum inhibitory concentration (MIC) values <10 μg mL(-1) , and total selectivity for Mycobacterium tuberculosis (Mtb) growth inhibition. A second set of 21 compounds bearing variations on ring C were synthesized and evaluated. This second library gave an additional six compounds displaying MIC values ≤10 μg mL(-1) and total selectivity for Mtb growth inhibition. These compounds serve as an excellent starting point for further development of Antitubercular therapies.
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Novel 1,4‐Substituted‐1,2,3‐Triazoles as Antitubercular Agents
ChemMedChem, 2015Co-Authors: Jarrad M Altimari, Samantha C Hockey, Helena I Boshoff, Andaleeb Sajid, Luke C HendersonAbstract:Tuberculosis (TB) remains a pressing unmet medical need, particularly with the emergence of multidrug-resistant and extensively drug-resistant tuberculosis. Here, a series of 1,4-substituted-1,2,3-triazoles have been synthesized and evaluated as potential Antitubercular agents. These compounds were assembled via click chemistry in high crude purity and in moderate to high yield. Of the compounds tested, 12 compounds showed promising Antitubercular activity with six possessing minimum inhibitory concentration (MIC) values