drug-resistant

Durlobactam sodium salt (ETX2514 sodium salt) is an inhibitor of β-lactamase with IC50 values of 4 nM, 14 nM, and 190 nM for Class A KPC-2, Class C AmpC, and Class D OXA-24, respectively. Durlobactam sodium salt can be used in studies about drug-resistant Gram-negative bacteria including Acinetobacter baumannii.

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.

WCK-5153 is an enhancer of β-Lactamase and an inhibitor of PBP2 with antimicrobial activities against Pseudomonas aeruginosa. WCK-5153 can be used in studies about the treatment of serious infections caused by highly drug-resistant Gram-negative pathogens.

3-(Trifluoromethyl)cinnamic acid (3-(3-(Trifluoromethyl)phenyl)acrylic acid) can be used to study drug-resistant bacterial infections.

Suprafenacine (N'-[(E)-(4-methylphenyl)methylidene]-4,5,6,7-tetrahydro-1H-indazole-3-carbohydrazide) is a cell-permeable microtubule destabilizer that induces cell cycle arrest and apoptosis in G2/M phase. Suprafenacine binds to microtubules and inhibits aggregation at the colchicine junction. Suprafenacine is selective for cancer cells, including drug-resistant cancer cells.

CHMFL-EGFR-202 is a potent, irreversible inhibitor of EGFR mutant kinase (IC50s: 5.3 nM and 8.3 nM for drug-resistant mutant EGFR T790M and WT EGFR kinases).

Anticonvulsant agent 2 is a potent orally active anticonvulsant that has shown antiepileptic activity in a model of drug-resistant epilepsy.

Artelinic acid is a water-soluble artemisinin analog with antimalarial activity and is used for the treatment of multi-drug resistant strains of Plasmodium falciparum.

GSK2556286 (GSK286) is an orally active inhibitor of Mycobacterium tuberculosis (M. tuberculosis).GSK2556286 inhibits the growth of human macrophages with an IC50 value of 0.07 μM.GSK2556286 is effective against both multidrug-resistant (MDR) or extensively drug-resistant (XDR) and drug-sensitive (DS) M. tuberculosis. GSK2556286 is effective against multi-drug resistant (MDR) or extensively drug resistant (XDR) and drug sensitive (DS) Mycobacterium tuberculosis.

Vamotinib (PF-114) is an orally active and specific tyrosine kinase inhibitor with antiproliferative and antitumour activity.Vamotinib inhibits the phosphorylation of BCR/ABL and BCR/ABL-T315I, which promotes apoptosis. Vamotinib is used to study drug-resistant Philadelphia chromosome-positive (Ph+) leukaemia and Alzheimer's disease.

9-dihydro-13-acetylbaccatin III (9-DHAB III)is an apoptosis inducer. It shows cytotoxicity against the MCF7 cell line and drug-resistant cell line MCF7-ADR.

1. Deoxyshikonin (Arnebin 7) may be a new drug candidate for wound healing and treatment of lymphatic diseases. 2. Deoxyshikonin enhances the ability of human dermal lymphatic microvascular endothelial cells (HMVEC-dLy) to undergo time-dependent in vitro cord formation. 3. Deoxyshikonin and dodecyl gallate show significantly synergic antimicrobial activity with penicillin in vivo and in vitro, and can effectively reduce nasopharyngeal and lung colonization caused by different penicillin-resistant pneumococcal serotypes.

Nifedipine (Procardia) is a dihydropyridine calcium channel blocking agent. Nifedipine inhibits the transmembrane influx of extracellular calcium ions into myocardial and vascular smooth muscle cells, causing dilatation of the main coronary and systemic arteries and decreasing myocardial contractility. This agent also inhibits the drug efflux pump P-glycoprotein which is overexpressed in some multi-drug resistant tumors and may improve the efficacy of some antineoplastic agents.

Rac-Belinostat (PX-105684) is a novel hydroxamic acid-type histone deacetylase (HDAC) inhibitor with antineoplastic activity. Belinostat targets HDAC enzymes, thereby inhibiting tumor cell proliferation, inducing apoptosis, promoting cellular differentiation, and inhibiting angiogenesis. This agent may sensitize drug-resistant tumor cells to other antineoplastic agents, possibly through a mechanism involving the down-regulation of thymidylate synthase.

Moxifloxacin (Avelox) is a fourth-generation fluoroquinolone that has been shown to be effective against Gram-positive, Gram-negative, and atypical strains, as well as multi-drug resistant Streptococcus pneumoniae.

1. Oroxylin A (Baicalein 6-methyl ether) has various anti-tumor effects including apoptosis, cell cycle arrest, drug-resistant reversion. 2. Oroxylin A possesses abilities of inhibiting the ATRA-induced IL-6 production via modulation of LAP/LIP/CHOP in leukemia cell lines, which could providing a therapeutic strategy for RAS. 3. Oroxylin A inhibits UCP2s triggers the MPTP opening, and promotes the apoptosis in CaCo-2 cells; uncoupling protein 2 plays a key role in mitochondrial apoptotic pathway. 4. Oroxylin A inhibits N1ICD translocating to the nucleus and binding to epithelial-mesenchymal transition-related transcription factor Snail, thus suppressing the invasion and migration of MCF-7 cells. 5. Oroxylin A improves the sensitivity of K562/ADM cells by increasing apoptosis in leukemic cells and decreasing the expression of CXCR4 and PI3K/Akt/NF-κB pathway, and probably served as a most promising agent for CML treatment.

DCZ0415 induces antimyeloma activity in vitro, in vivo and in primary cells of drug-resistant myeloma patients. DCZ0415 is a potent TRIP13 inhibitor that can impair the repair of non-homologous end junctions and inhibit NF-κB activity.

Clovibactin, a novel antibiotic, effectively eradicates drug-resistant bacterial pathogens and demonstrates no discernible resistance. It is derived from uncultured soil bacteria [1].

3-O-(E)-p-coumaroyl tormentic acid may be promising lead compound for developing an effective drug for treatment of leukemia, it induces apoptotic cell death in human leukemia (HL60) via mainly mitochondrial pathway by, at least in part, Topo I inhibition. 3-O-trans-p-coumaroyltormentic acid shows cytotoxicity against four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15) in vitro, the IC50 values of 13.72, 14.29,14.61, 14.04 uM, respectively. 3beta-O-cis-p-Coumaroyltormentic acid, and 3beta-O-trans-p-coumaroyltormentic acid are weakly selective for vancomycin-resistant Enterococcus (VRE) compared with eukaryotic cells, with an MIC of 59.4microg/mL and a 50% inhibitory concentration (IC50) of 72.0microg/mL for monkey kidney epithelial (MA104) cells. A mixture of 3-O-cis-p-coumaroyltormentic acid and 3-O-trans-p-coumaroyltormentic acid shows an inhibitory effect comparable to (-)-epigallocatechin gallate (EGCG) of green tea on the activation of Epstein-Barr virus early antigen (EBV-EA) induced by 12-O-tetradeca--noylphorbol-13-acetate (TPA).

Isogambogic acid shows cytotoxic activiity against KB and drug-resistant KB-V1 cell lines.

FIT-039 is a selective and ATP-competitive, orally active inhibitor of CDK9( IC50 : 5.8 μM;CDK9/cyclin T1). FIT-039 inhibits replication of HSV-1 (IC50 of 0.69 μM), HSV-2, human adenovirus, and human CMV. FIT-039 is a promising antiviral agent for inhibiting drug-resistant HSVs and other DNA viruses.

Jatrophane 5 demonstrates the most powerful inhibition of P-gp, higher than R(+)-verapamil and tariquidar in colorectal multi-drug resistant (MDR) cells (DLD1-TxR).

ATP Synthesis-IN-1 (Compound 4), a quinoline derivative, potently inhibits PA ATP synthesis with an IC50 of 11.1μg/mL and exhibits antibacterial properties. This compound is utilized in studying drug-resistant PA infections [1].

Benzyldodecyldimethylammonium chloride dihydrate can be used as an insecticide reagent. It can target drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus, multidrug-resistant Pseudomonas aeruginosa, etc., in a concentration-dependent manner.

Poly(I:C):Kanamycin (1:1) sodium is a symmetric complex combining Poly(I:C) sodium, a synthetic double-stranded RNA analog acting as a TLR3 and RIG-I/MDA5 agonist, with Kanamycin, an antibacterial agent effective against both Gram-negative and positive bacteria by inhibiting translocation and causing miscoding on the 70S ribosomal subunit. Poly(I:C) sodium serves as a potent vaccine adjuvant, bolstering innate and adaptive immunity and prompting apoptosis in cancer cells [1] [2]. Meanwhile, Kanamycin exhibits significant efficacy against Mycobacterium tuberculosis, including drug-resistant strains, and Klebsiella pneumoniae, offering valuable insights for tuberculosis and pneumonia research [3] [4] [5] [6].

Chlorido[N,N'-disalicylidene-1,2-phenylenediamine]iron(III) is an inducer of ferroptosis.1 It induces ferroptosis, but not apoptosis or necroptosis, in NB1 cancer cells when used at a concentration of 3 μM.1 Chlorido[N,N'-disalicylidene-1,2-phenylenediamine]iron(III) inhibits proliferation of BJAB, NALM-6, Jurkat, MelHO, and MCF-7 cancer cells (IC50s = 0.07, 2.5, 1.5, 3, and 5 μM, respectively), as well as NALM-6 cells resistant to daunorubicin and vincristine when used at concentrations ranging from 0.04 to 0.125 μM.2 |1. Sagasser, J., Ma, B., Baecker, D., et al. A new approach in cancer treatment: Discovery of chlorido[N,N'-disalicylidene-1,2-phenylenediamine]iron(III) complexes as ferroptosis inducers. J. Med. Chem. 62(17), 8053-8061 (2019).|2. Lee, S.-Y., Hille, A., Kitanovic, I., et al. [FeIII(salophene)Cl], a potent iron salophene complex overcomes multiple drug resistance in lymphoma and leukemia cells. Leuk. Res. 35(3), 387-393 (2011).

Kazinol A shows strong inhibition of arachidonic acid (AA)-induced platelet aggregation. It also exhibits potent inhibition with IC50 values ranging 0.6-164 M against XOD. Kazinol A may be a candidate for the development of effective anti-cancer drug on h

Wulignan A1 exhibits activity against leukemia P-388 in vitro; it also may have anti-influenza virus H1N1 and H1N1-TR (a Tamiflu drug resistant virus strain) activities.

Ardisiacrispin B displays cytotoxic effects in multi-factorial drug resistant cancer cells via ferroptotic and apoptotic cell death.

Benzquinamide (P2647), an antiemetic agent with anticancer activity, inhibits p-glycoprotein-mediated drug efflux and potentiates the cytotoxicity of anticancer drugs in multidrug-resistant cells.The Ki values of Benzquinamide for α2A, α2B, and α2C adrenergic receptor (α2-AR) were 1,365, 691, and 545 nM, respectively. 545 nM, respectively.

GSK1733953A can be used as a small molecule Mycobacterium tuberculosis respiration inhibitor with an inhibitory effect on MenG activity and an IC50 value of 2.6 ± 0.6 μM.GSK1733953A is a selective biphenylbenzamide with an inhibitory effect on the catalytic methylation of the Mycobacterium tuberculosis desmethylnaphthoquinone methyltransferase, and the MIC of GSK1733953A against Mycobacterium tuberculosis H4Rv was 8.37 μg/ml. MIC of 8.37 μg/ml and MIC of 1.2 to 9.6 μg/ml against drug-resistant strains.GSK1733953A is a candidate compound for the treatment of tuberculosis.

Arborinine shows mild in vitro antibacterial activity, it possesses moderate levels of anti-hepatitis C virus(HCV) activities with the IC50 values being 6.4 ± 0.7 ug/ml. Arborinine shows antifeedant activity against Spodoptera frugiperda. Arborinin shows

OY-101, an orally active compound, serves as a potent and specific inhibitor of P-glycoprotein (P-gp). It has the capability to sensitize drug-resistant tumors and counteract tumor multidrug resistance efficiently. Compared to Tetrandrine [1], OY-101 demonstrates enhanced water-solubility, cytotoxicity, and reversal activity.

4,5-Dimethoxycanthin-6-one is an alkaloid isolated from Picrasma quassioides BENNET (Simaroubaceae).4,5-Dimethoxycanthin-6-one was isolated from Picrasma quassioides BENNET (Simaroubaceae) with antimicrobial activity.4,5-Dimethoxycanthin-6-one was isolated from Picrasma quassioides BENNET (Simaroubaceae) with antimicrobial activity. Dimethoxycanthin-6-one is a potent, non-competitive inhibitor of CYP1A2-mediated phenacetin O-deethylation (IC50: 1.7 μM, Ki: 2.6 μM), and a potent inhibitor of cyclic adenosine monophosphate (cAMP) phosphodiesterase.4,5-(4,5-Dimethoxycanthin-6-one) is an alkaloid isolated from Picrasma quassioides BENNET (Simaroubaceae). 4,5-Dimethoxycanthin-6-one has antimicrobial activity against Staphylococcus aureus and its drug-resistant strains.4,5-Dimethoxycanthin-6-one is cytotoxic to the tumor cell lines U937 and HepG2.4,5-Dimethoxycanthin-6-one is a cytotoxicity inhibitor (IC50 : Ki : 6 μM, Ki : 6 μM).

Zndm19 is an inhibitor of New Delhi Metallo-β-lactamase-1 (NDM-1), utilized in researching drug-resistant bacterial infections [1].

Staphyloferrin A, a siderophore, can be utilized in conjunction with antibiotics to investigate drug-resistant bacteria implicated in skin diseases [1].

Taxinine and Taxinine B can inhibit the drug transport by P-glycoprotein in multidrug-resistant cells.

iKIX1 is an Pdr1-dependent gene activation. It re-sensitizes drug-resistant C. glabrata to azole antifungals in vitro and in animal models for disseminated and urinary tract C. glabrata infection.

Thiocarlide (isoxyl) is a thiourea derivative that was used in the 1960s to successfully treat tuberculosis (TB). It has considerable antimycobacterial activity in vitro and is effective against multi-drug resistant strains of Mycobacterium tuberculosis in the range of 1-10 µg/ml. [1] [2] At concentrations of 10 µM, isoxyl inhibits the synthesis of M. bovis during six hours of exposure which is similar to isoniazid (INH) and ethionamide (ETH), two other predominant anti-tuberculosis drugs. Unlike INH and ETH, isoxyl also partially inhibits the synthesis of fatty acids. Isoxyl shows no acute toxicity against primary macrophage cell cultures as demonstrated by diminution of redox activity.[2]

Imperialine 3-β-D-glucoside (Sipeimine-3-beta-D-glucoside) is a natural product. Imperialine 3-β-D-glucoside may exhibit anti-tumor properties against multi-drug resistant tumor cells.

Antitubercular agent-39 (Compound P1) is a potent agent effective against both drug-resistant strains and drug-susceptible clinical isolates of tuberculosis, exhibiting inhibition of the Mtb strain H37Rv with a minimum inhibitory concentration (MIC) of less than 1 μM [1].

HIV-1 protease-IN-11 (compound 34a), an HIV-1 protease inhibitor, demonstrates potent inhibition with an IC50 of 0.41 nM and maintains substantial efficacy against drug-resistant variant [1].

Nemorosone is a polycyclic polyprenylated acylphloroglucinol (PPAP) originally isolated from C. rosea that has antiproliferative properties.1 Nemorosone inhibits growth of NB69, Kelly, SK-N-AS, and LAN-1 neuroblastoma cells (IC50s = 3.1-6.3 μM), including several drug-resistant clones, but not MRC-5 human embryonic fibroblasts (IC50 = >40 μM).2 It increases DNA fragmentation in LAN-1 cells in a dose-dependent manner, and decreases N-Myc protein levels and phosphorylation of ERK1/2 by MEK1/2. Nemorosone also inhibits growth of Capan-1, AsPC-1, and MIA-PaCa-2 pancreatic cancer cells (IC50s = 4.5-5.0 μM following a 72-hour treatment) but not human dermal and foreskin fibroblasts (IC50s = >35 μM).1 It induces apoptosis, abolishes the mitochondrial membrane potential, and increases cytosolic calcium concentration in pancreatic cancer cells in a dose-dependent manner. Nemorosone activates the caspase cascade in a dose-dependent manner and inhibits cell cycle progression, increasing the proportion of cells in the G0/G1 phase, in both neuroblastoma and pancreatic cancer cells.1,2 Nemorosone (50 mg/kg, i.p., per day) also reduces tumor growth in an MIA-PaCa-2 mouse xenograft model.3References1. Holtrup, F., Bauer, A., Fellenberg, K., et al. Microarray analysis of nemorosone-induced cytotoxic effects on pancreatic cancer cells reveals activation of the unfolded protein response (UPR). Br. J. Pharmacol. 162(5), 1045-1059 (2011).2. Díaz-Carballo, D., Malak, S., Bardenheuer, W., et al. Cytotoxic activity of nemorosone in neuroblastoma cells. J. Cell. Mol. Med. 12(6B), 2598-2608 (2008).3. Wold, R.J., Hilger, R.A., Hoheisel, J.D., et al. In vivo activity and pharmacokinetics of nemorosone on pancreatic cancer xenografts. PLoS One 8(9), e74555 (2013). Nemorosone is a polycyclic polyprenylated acylphloroglucinol (PPAP) originally isolated from C. rosea that has antiproliferative properties.1 Nemorosone inhibits growth of NB69, Kelly, SK-N-AS, and LAN-1 neuroblastoma cells (IC50s = 3.1-6.3 μM), including several drug-resistant clones, but not MRC-5 human embryonic fibroblasts (IC50 = >40 μM).2 It increases DNA fragmentation in LAN-1 cells in a dose-dependent manner, and decreases N-Myc protein levels and phosphorylation of ERK1/2 by MEK1/2. Nemorosone also inhibits growth of Capan-1, AsPC-1, and MIA-PaCa-2 pancreatic cancer cells (IC50s = 4.5-5.0 μM following a 72-hour treatment) but not human dermal and foreskin fibroblasts (IC50s = >35 μM).1 It induces apoptosis, abolishes the mitochondrial membrane potential, and increases cytosolic calcium concentration in pancreatic cancer cells in a dose-dependent manner. Nemorosone activates the caspase cascade in a dose-dependent manner and inhibits cell cycle progression, increasing the proportion of cells in the G0/G1 phase, in both neuroblastoma and pancreatic cancer cells.1,2 Nemorosone (50 mg/kg, i.p., per day) also reduces tumor growth in an MIA-PaCa-2 mouse xenograft model.3 References1. Holtrup, F., Bauer, A., Fellenberg, K., et al. Microarray analysis of nemorosone-induced cytotoxic effects on pancreatic cancer cells reveals activation of the unfolded protein response (UPR). Br. J. Pharmacol. 162(5), 1045-1059 (2011).2. Díaz-Carballo, D., Malak, S., Bardenheuer, W., et al. Cytotoxic activity of nemorosone in neuroblastoma cells. J. Cell. Mol. Med. 12(6B), 2598-2608 (2008).3. Wold, R.J., Hilger, R.A., Hoheisel, J.D., et al. In vivo activity and pharmacokinetics of nemorosone on pancreatic cancer xenografts. PLoS One 8(9), e74555 (2013).

6-Prenylindole is a bacterial metabolite that has been found in Streptomyces and has antifungal and antimalarial properties.1 It is active against A. brassicicola strain TP-F0423 and F. oxysporum f. sp. tulipae TU-4-2 (15 and 30 μg/disc in the paper disc assay), and also drug-resistant P. falciparum strain K1 (IC50 = 21 μg/ml).2 |1. Sasaki, T., Igarashi, Y., Ogawa, M., et al. Identification of 6-prenylindole as an antifungal metabolite of Streptomyces sp. TP-A0595 and synthesis and bioactivity of 6-substituted indoles. J. Antibiot. (Tokyo) 55(11), 1009-1012 (2002).|2. Nkunya, M.H., Makangara, J.J., and Jonker, S.A. Prenylindoles from Tanzanian Monodora and Isolona species. Nat. Prod. Res. 18(3), 253-258 (2004).

U 95133 is a potent, broad-spectrum nonnucleoside reverse transcriptase inhibitor of drug-resistant isolates of human immunodeficiency virus type 1.

DB07107 is a potent inhibitor of drug resistant T315I mutant Bcr-Abl tyrosine kinase and a potent Akt1 inhibitor (IC50: 360 nM).

Compound 9C [c[Arg-Arg-Arg-Arg-Nal-Nal-Nal]] demonstrates broad-spectrum efficacy against drug-resistant Gram-positive and Gram-negative bacteria. It exhibits minimum inhibitory concentrations (MICs) of 3.1 μg/mL for MRSA (ATCC BAA-1556), 3.1 μg/mL for S. aureus (ATCC 29213), 12.5 μg/mL for P. aeruginosa (ATCC 27883), and 25 μg/mL for E. coli (ATCC 25922) [1].

MRT-2359 is a potent and orally available GSPT1 reducer with antitumour activity.MRT-2359 inhibits the growth of drug-resistant non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) cells.MRT-2359 exhibits preferential activity in MYC-driven cell lines.

CGI-17341 is an orally active representative of the 5-nitroimidazole series of antimicrobial agents. CGI 17341 inhibits the drug-susceptible and multi-drug-resistant strains of Mycobacterium tuberculosis at concentrations ranging from 0.1 to 0.3 microgram

ACT-451840 is a drug of antimalarial activity. It has effective activity against sensitive and resistant Plasmodium falciparum strains.