The Experts below are selected from a list of 228 Experts worldwide ranked by ideXlab platform
Haridas B. Rode - One of the best experts on this subject based on the ideXlab platform.
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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, Sunil Misra, Sidharth Chopra, Dharmarajan Sriram, Eruva Vamshi Krishna, Balakrishnan Mahizhaveni, Vijayan N Azger Dusthackeer, 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.
William R. Bishai - One of the best experts on this subject based on the ideXlab platform.
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Preliminary Structure–Activity Relationships and Biological Evaluation of Novel Antitubercular Indolecarboxamide Derivatives Against Drug-Susceptible and Drug-Resistant Mycobacterium tuberculosis Strains
2016Co-Authors: Oluseye K. Onajole, Marco Pieroni, Suresh K. Tipparaju, Shichun Lun, Jozef Stec, Gang Chen, Hendra Gunosewoyo, Haidan Guo, Nicole C. Ammerman, William R. BishaiAbstract:Tuberculosis (TB) remains one of the leading causes of mortality and morbidity worldwide, with approximately one-third of the world’s population infected with latent TB. This is further aggravated by HIV coinfection and the emergence of multidrug- and extensively drug-resistant (MDR and XDR, respectively) TB; hence the quest for highly effective Antitubercular drugs with novel modes of action is imperative. We report herein the discovery of an indole-2-carboxamide analogue, 3, as a highly potent Antitubercular Agent, and the subsequent chemical modifications aimed at establishing a preliminary body of structure–activity relationships (SARs). These efforts led to the identification of three molecules (12–14) possessing an exceptional activity in the low nanomolar range against actively replicating Mycobacterium tuberculosis, with minimum inhibitory concentration (MIC) values lower than those of the most prominent Antitubercular Agents currently in use. These compounds were also devoid of apparent toxicity to Vero cells. Importantly, compound 12 was found to be active against the tested XDR-TB strains and orally active in the serum inhibition titration assay
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Preliminary Structure–Activity Relationships and Biological Evaluation of Novel Antitubercular Indolecarboxamide Derivatives Against Drug-Susceptible and Drug-Resistant Mycobacterium tuberculosis Strains
Journal of medicinal chemistry, 2013Co-Authors: Oluseye K. Onajole, Marco Pieroni, Suresh K. Tipparaju, Shichun Lun, Jozef Stec, Gang Chen, Hendra Gunosewoyo, Haidan Guo, Nicole C. Ammerman, William R. BishaiAbstract:Tuberculosis (TB) remains one of the leading causes of mortality and morbidity worldwide, with approximately one-third of the world’s population infected with latent TB. This is further aggravated by HIV coinfection and the emergence of multidrug- and extensively drug-resistant (MDR and XDR, respectively) TB; hence the quest for highly effective Antitubercular drugs with novel modes of action is imperative. We report herein the discovery of an indole-2-carboxamide analogue, 3, as a highly potent Antitubercular Agent, and the subsequent chemical modifications aimed at establishing a preliminary body of structure–activity relationships (SARs). These efforts led to the identification of three molecules (12–14) possessing an exceptional activity in the low nanomolar range against actively replicating Mycobacterium tuberculosis, with minimum inhibitory concentration (MIC) values lower than those of the most prominent Antitubercular Agents currently in use. These compounds were also devoid of apparent toxicity ...
Vitthal B. Makane - One of the best experts on this subject based on the ideXlab platform.
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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, Sunil Misra, Sidharth Chopra, Dharmarajan Sriram, Eruva Vamshi Krishna, Balakrishnan Mahizhaveni, Vijayan N Azger Dusthackeer, 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.
Ken Umehara - One of the best experts on this subject based on the ideXlab platform.
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erratum for sasabe et al Antitubercular Agent delamanid and metabolites as substrates and inhibitors of abc and solute carrier transporters
Antimicrobial Agents and Chemotherapy, 2016Co-Authors: Hiroyuki Sasabe, Yoshihiko Shimokawa, Masakazu Shibata, Kenta Hashizume, Yusuke Hamasako, Yoshihiro Ohzone, Eiji Kashiyama, Ken UmeharaAbstract:Volume 60, no. 6, p. [3497–3508][1], 2016. Page 3507, left column, lines 2 and 3: “nonnucleoside reverse transcriptase inhibitors (e.g., zidovudine)” should read “nucleoside reverse transcriptase inhibitors (e.g., zidovudine).” [1]: /lookup/doi/10.1128/AAC.03049-15
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Antitubercular Agent delamanid and metabolites as substrates and inhibitors of abc and solute carrier transporters
Antimicrobial Agents and Chemotherapy, 2016Co-Authors: Hiroyuki Sasabe, Yoshihiko Shimokawa, Masakazu Shibata, Kenta Hashizume, Yusuke Hamasako, Yoshihiro Ohzone, Eiji Kashiyama, Ken UmeharaAbstract:Delamanid (Deltyba, OPC-67683) is the first approved drug in a novel class of nitro-dihydro-imidazooxazoles developed for the treatment of multidrug-resistant tuberculosis. Patients with tuberculosis require treatment with multiple drugs, several of which have known drug-drug interactions. Transporters regulate drug absorption, distribution, and excretion; therefore, the inhibition of transport by one Agent may alter the pharmacokinetics of another, leading to unexpected adverse events. Therefore, it is important to understand how delamanid affects transport activity. In the present study, the potencies of delamanid and its main metabolites as the substrates and inhibitors of various transporters were evaluated in vitro Delamanid was not transported by the efflux ATP-binding cassette (ABC) transporters P-glycoprotein (P-gp; MDR1/ABCB1) and breast cancer resistance protein (BCRP/ABCG2), solute carrier (SLC) transporters, organic anion-transporting polypeptides, or organic cation transporter 1. Similarly, metabolite 1 (M1) was not a substrate for any of these transporters except P-gp. Delamanid showed no inhibitory effect on ABC transporters MDR1, BCRP, and bile salt export pump (BSEP; ABCB11), SLC transporters, or organic anion transporters. M1 and M2 inhibited P-gp- and BCRP-mediated transport but did so only at the 50% inhibitory concentrations (M1, 4.65 and 5.71 μmol/liter, respectively; M2, 7.80 and 6.02 μmol/liter, respectively), well above the corresponding maximum concentration in plasma values observed following the administration of multiple doses in clinical trials. M3 and M4 did not affect the activities of any of the transporters tested. These in vitro data suggest that delamanid is unlikely to have clinically relevant interactions with drugs for which absorption and disposition are mediated by this group of transporters.
Manojit Pal - One of the best experts on this subject based on the ideXlab platform.
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Construction and functionalization of fused pyridine ring leading to novel compounds as potential Antitubercular Agents
Bioorganic & medicinal chemistry letters, 2012Co-Authors: Balakrishna Dulla, Baojie Wan, Scott G. Franzblau, Ravikumar Kapavarapu, Oliver Reiser, Javed Iqbal, Manojit PalAbstract:A series of fused and functionalized pyridine derivatives were designed, synthesized and tested for their potential Antitubercular properties. All these novel compounds were prepared by using multistep methods involving the construction of pyridine ring as a key synthetic step. Some of these compounds were found to be interesting when tested for their Antitubercular properties in vitro and one of them appeared as an attractive and potential Antitubercular Agent.