Tuberculosis inhibitor 1

Tuberculosis inhibitor 1 is a potent, non-cytotoxic inhibitor of Trypanosoma brucei growth [EC50: 5 nM].

Tuberculosis Inhibitor 12, an oxadiazole derivative, effectively inhibits Mycobacterium tuberculosis, demonstrating inhibition rates of 82% and 78% at a concentration of 20 μM on 7H9-Tw-OADC media, respectively [1].

Compound 14, also known as Tuberculosis Inhibitor 11, enhances the antimycobacterial efficacy of antitubercular agent [1].

Tuberculosis Inhibitor 10 moderately inhibits the enzyme MSMEG_6649 and potentiates the antimycobacterial activity of PAS [1].

LeuRS-IN-1 is an orally active and potent Mycobacterium tuberculosis leucyl-tRNA synthetase inhibitor with anti-leukemic and anti-malarial activity, inhibits M.tb LeuRS, inhibits HepG2 protein synthesis, and can be used in leukemia research.

D-Cycloserine (RO-1-9213) is a broad spectrum antibiotic used as a second line agent for treatment of drug resistant tuberculosis, always in combination with other antituberculosis agents.

LeuRS-IN-1 hydrochloride is an orally active and highly potent inhibitor of Mycobacterium tuberculosis leucyl-tRNA synthetase with anti-leukemic activity and anti-malarial activity, inhibits M.tb LeuRS, inhibits HepG2 protein synthesis, and can be used in the study of leukemia.

1. Kuwanon G (Moracenin B) as dual inhibitors of PTP1B and α-glucosidase enzymes, as well as insulin sensitizers, it may potentially be utilized as an effective treatment for Type II diabetes mellitus. 2. Kuwanon G has anti-inflammatory activity, it can attenuate atherosclerosis through inhibiting foam cell formation and inflammatory response. 3. Kuwanon G is a potent inhibitor of Mycobacterium tuberculosis protein tyrosine phosphatase B. 4. Kuwanon G shows acetylcholinesterase (AChE) and butyrylcholinesterase(BChE) inhibitory activities, it may be a promising candidate for preventive and therapeutic agents for Alzheimer's disease. 5. Kuwanon G prevents the pathological progression of allergic asthma through the inhibition of lung destruction by inflammation and immune stimulation. 6. Kuwanon G has antibacterial activity against oral pathogens. 7. Kuwanon G is a specific antagonist for the GRP-preferring receptor and can be useful for studying the physiological and pathological role of GRP.

TBA-7371 (DprE1-IN-1) is a potent inhibitor of DprE1 and PDE6.

MenA-IN-2 is a potent 1, 4-dihydroxy-2-naphthoate isopentadiene transferase (MenA) inhibitor with an IC50 value of 22 µM for MenA and 10 µM for Mycobacterium tuberculosis (Mtb). The continuous transmission of MenA-IN-2 Mtb has inhibitory effect.

FadD32 inhibitor -1 has anti-tuberculosis activity and is an effective FadD32 inhibitor.

MtbHU-IN-1 is a Mycobacterium tuberculosis nucleoid-associated protein HU (MtbHU)inhibitor(binding to WT MtbHU with a Kd of 98 nM).

Norverapamil hydrochloride (D591 hydrochloride) ((±)-Norverapamil hydrochloride) is an N-demethylated metabolite of Verapamil and it is an L-type calcium channel blocker and a P-glycoprotein (P-gp) function inhibitor.

VEGFR-2 InhA-IN-1, a dual inhibitor based on pyrazole, targets InhA and VEGFR, exhibiting both anti-tuberculosis and anti-angiogenic properties. It demonstrates effective antibacterial activity against the Mycobacterium tuberculosis H37Rv strain (MIC = 6.25 μg mL) and significantly suppresses VEGFR-2 activity (IC 50 = 15.27 nM).

InhA-IN-8 (compound 6c) serves as an orally effective inhibitor of the Mycobacterium tuberculosis enzyme InhA (enoyl-ACP reductase). This compound demonstrates robust inhibitory activity against Mtb H37Rv, with a minimum inhibitory concentration (MIC) ranging from 0.5 to 1 μg mL. Additionally, InhA-IN-8 is utilized in studies involving acute tuberculosis models in mice.

Soulattrolide, a naturally occurring coumarin synthesized by Calophyllum (Calophyllaceae) rainforest tree leaves, acts as a potent inhibitor of reverse transcriptase from HIV-1 (RT-HIV-1) and exhibits activity against Mycobacterium tuberculosis.

Biotin protein ligase-IN-1 (Compound Bio-9) is an inhibitor of biotin protein ligase (BPL) with a Kd of 7 nM. This compound exhibits antimicrobial activity, with minimum inhibitory concentration (MIC) values of 0.2 μM against Staphylococcus aureus (including MRSA and MSSA) and 20 μM against Mycobacterium tuberculosis.

Pks13-IN-1 (Compound 44) is an orally active inhibitor of Mycobacterium tuberculosis polyketide synthase 13 (Pks13). It inhibits the M. tuberculosis H37Rv strain with a minimum inhibitory concentration (MIC) of 0.07 μM. In mouse models, Pks13-IN-1 demonstrates antibacterial activity.

DXR-IN-4 (Compound 12a) is an inhibitor of 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR). It effectively inhibits DXR in Plasmodium falciparum, Escherichia coli, and Mycobacterium tuberculosis, with IC50 values for PfDXR, EcDXR, and MtDXR at 18, 4.9, and 89 nM, respectively. Additionally, DXR-IN-4 demonstrates antimalarial activity against Plasmodium falciparum strains 3D7 and Dd2, with IC50 values of 11 μM and 12 μM.

Mtb against-1 (compound 17af) is an inhibitor of Mycobacterium tuberculosis, demonstrating an IC90 of 1.2 μM against wild-type strains and 0.9 μM against low-permeability LepB strains.

BioA-IN-1 (Compound 15) is an inhibitor of the key enzyme BioA in the biotin biosynthesis pathway of Mycobacterium tuberculosis, with an IC50 value of 0.195 μM. It exhibits antibacterial activity without cytotoxicity.

10-DEBC hydrochloride, a selective Akt inhibitor demonstrating an IC50 value of 1.28 μM, is identified as a novel anti-tuberculosis compound [1] [2].

OPC-167832 is a potent and orally active dprE1 Inhibitor with an IC50 of 0.258 μM. OPC-167832 has antituberculosis activity and can be used for the research of tuberculosis caused by Mycobacterium tuberculosis[1]. OPC-167832 exhibits very low MICs against laboratory strains of M. tuberculosis H37Rv (MIC: 0.0005 μg/ml) and Kurono (MIC: 0.0005 μg/ml) and strains with monoresistance to rifampin (RIF), isoniazid (INH), ethambutol (EMB), streptomycin (STR), and pyrazinamide (PZA) (MIC: 0.00024-0.001 μg/ml). However, OPC-167832 has minimal or no activity against standard strains of nonmycobacterial aerobic and anaerobic bacteria[1].The IC90 values of OPC-167832 against intracellular M. tuberculosis strains H37Rv and Kurono are 0.0048 and 0.0027 μg/ml, respectively. OPC-167832 shows bactericidal activity against intracellular M. tuberculosis at a low concentration, and the bactericidal activity is saturated at concentrations of 0.004 μg/ml or higher[1]. OPC-167832 (oral administration; 0.625-10 mg/kg) exhibits a good pharmacokinetic characteristic. The plasma reaches peak at 0.5 h to 1.0 h (tmax) and is eliminated with a half-life (t1/2) of 1.3 h to 2.1 h OPC-167832 distribution in the lungs is approximately 2 times higher than that in plasma, and the Cmax and AUCt of OPC-167832 in plasma and the lungs shows dose dependency[1].OPC-167832 (oral administration; 0.625-10 mg/kg; 4 weeks) significantly reduces lung CFU compared to the vehicle group. The dose-dependent decrease of lung CFU is observed from 0.625 mg/kg to 2.5 mg/kg. In a M. tuberculosis Kurono-infected ICR female mice model. OPC-167832 combines with DMD, BDQ, or LVX via oral gavage exhibits significantly higher efficacies than each single agent alone[1].[1].OPC-167832 (oral gavage; 2.5 mg/kg; combination with DCMB; 12 weeks) demonstrates the most potent efficacy when compares with DC, DCB. The lung CFU count after 6 weeks of treatment is below the detection limit, and at the end of just 8 weeks of treatment, the bacteria in the lungs of all the evaluated mice had already been eradicate[1]. [1]. Norimitsu Hariguchi, et al. OPC-167832, a Novel Carbostyril Derivative with Potent Antituberculosis Activity as a DprE1 Inhibitor.Antimicrob Agents Chemother. 2020 May 21;64(6):e02020-19.

S.pombe lumazine synthase-IN-1 is a compound that inhibits lumazine synthases, with Ki values of 243 μM for Schizosaccharomyces pombe and 9.6 μM for Mycobacterium tuberculosis, respectively[1].