TABLE 1 .
Nontoxic host-targeting inhibitors of four intracellular pathogensa
| Compound name | Therapeutic class | Inhibition |
Major pathway/target | |||
|---|---|---|---|---|---|---|
| Cb | Lp | Ba | Rc | |||
| Trifluoperazine⋅2HCl (205) | Antipsychotic | × | × | × | GPCRs/Ca | |
| Lomerizine (330) | Antimigraine | × | × | × | Ca | |
| Bepridil⋅HCl (12) | Antianginal | × | × | × | Ca | |
| Loperamide⋅HCl (16) | Antidiarrheal | × | × | × | GPCRs/Ca | |
| (+)-Butaclamol⋅HCl (93), aripiprazole (149), trifluperidol (637) | Antipsychotic | × | × | × | GPCRs/Ca | |
| Clemastine (130) | Antihistamine | × | × | × | GPCRs | |
| Nisoldipine (139) | Antihypertensive | × | × | × | GPCRs/Ca | |
| Mifepristone (620) | Abortifacient | × | × | S | ||
| Oxatomide (223) | Antiallergic | × | × | GPCRs | ||
| Amitriptyline⋅HCl (444) | Antidepressant | × | × | GPCRs | ||
| Chlorpromazine⋅HCl (95) | Antiemetic | × | × | GPCRs/Ca | ||
| Cyproheptadine (639) | Antihistamine | × | × | GPCRs/Ca | ||
| Trequinsin⋅HCl (609) | Antihypertensive | × | × | GPCRs/Ca | ||
| Bromocriptine mesylate (215) | Anti-Parkinsonian | × | × | GPCRs | ||
| Spiperone⋅HCl (107) | Antipsychotic | × | × | GPCRs/Ca | ||
| Dihydroergocristine (594) | Antivertigo | × | × | GPCRs | ||
| Finasteride (440) | Benign prostatic hypertrophy | × | × | S | ||
| Melengestrol acetate (622) | Progestogen | × | × | S | ||
| Fluoxetine (596) | Antidepressant | × | × | GPCRs/Ca | ||
| Verapamil (198), felodipine (202) | Antihypertensive | × | × | GPCRs/Ca | ||
| Naltrindole⋅HCl (105) | Opioid antagonist | × | × | GPCRs | ||
| Orphenadrine citrate (402) | Antispasmodic | × | × | GPCRs | ||
| Desloratadine (412) | Antihistamine | × | × | GPCRs | ||
| Donepezil⋅HCl (5) | Nootropic | × | GPCRs | |||
| Amiodarone⋅HCl (13) | Antiarrhythmic | × | IonC | |||
| Benzydamine (640) | Analgesic | × | Lipids | |||
| Suramin (256) | Anthelmintic | × | GPCRs | |||
| Flutamide (448) | Antiandrogen | × | GPCRs | |||
| Propafenone (24) | Antiarrhythmic | × | GPCRs | |||
| Ketotifen (587) | Antiasthmatic | × | GPCRs/Ca | |||
| Maprotiline⋅HCl (55), nisoxetine⋅HCl (56), mianserin⋅HCl (81), imipramine⋅HCl (113), amoxapine (114), escitalopram (153), citalopram (394) | Antidepressant | × | GPCRs/Ca | |||
| Domperidone (96), tropisetron (577) | Antiemetic | × | GPCRs | |||
| Danazol (410) | Antigonadotropin | × | S | |||
| Promethazine⋅HCl (103), loratadine (478) | Antihistamine | × | GPCRs | |||
| Nicardipine⋅HCl (14), naftopidil⋅2HCl (33), manidipine (135), lacidipine (140), propranolol S(−) (163), diltiazem (194), nimodipine (196), nitrendipine (197), cilnidipine (203), doxazosin (419), propranolol (540) | Antihypertensive | × | GPCRs/Ca | |||
| Dihydroergotamine mesylate (40) | Antimigraine | × | GPCRs | |||
| Lapatinib ditosylate (274), bicalutamide (305), toremifene (570) | Antineoplastic | × | HER, TK, GPCRs | |||
| Calcipotriene (283) | Antipsoriatic | × | Vitamin D | |||
| Haloperidol (67), quetiapine fumarate (111), clozapine (216), clothiapine (217), mesoridazine besylate (600) | Antipsychotic | × | GPCRs/Ca | |||
| Dipyridamole (227), cilostamide (602) | Antithrombotic | × | PDE | |||
| Canrenone (380) | Diuretic | × | S | |||
| Vardenafil (131) | Erectile dysfunction | × | PDE | |||
| Estradiol (428) | Estrogen | × | S | |||
| Naltriben methanesulfonate hydrate (118) | Opioid antagonist | × | GPCRs | |||
| Chlormadinone acetate (388), progesterone (523) | Progestogen | × | S | |||
| Cinanserin (592) | Serotonin antagonist | × | GPCRs | |||
| Flunarizine⋅2HCl (200) | Vasodilator | × | GPCRs/Ca | |||
| Fluspirilene (17) | Antipsychotic | × | × | GPCRs/Ca | ||
| (R)-(−)-Apomorphine⋅HCl (94) | Anti-Parkinsonian | × | GPCR | |||
| Carvedilol (164), telmisartan (558) | Antihypertensive | × | GPCRs/Ca, ATR/PPAR | |||
| Bleomycin (158), 5-fluorouracil (441) | Antineoplastic | × | DNA | |||
| Raloxifene (262) | Antiosteoporotic | × | S | |||
| Tolcapone (136) | Anti-Parkinsonian | × | COMT | |||
| Estriol (429), medroxyprogesterone 17-acetate (482), pregnenolone (527), megestrol acetate (621) | Estrogen/progestogen | × | S | |||
| Clomiphene (398) | Gonad stimulant | × | × | S | ||
| Dehydroepiandrosterone (411) | Adrenal hormone | × | S | |||
| Dexamethasone (226), clobetasol propionate (401), fluocinolone acetonide (446) | Anti-inflammatory | × | S, GCR | |||
| Doxofylline (421) | Bronchodilator | × | PDE | |||
| 17-Hydroxyprogesterone (463) | Progestogen | × | S | |||
| Prazosin⋅HCl (34) | Antihypertensive | × | GPCRs | |||
| Troglitazone (260) | Antidiabetic | × | PPAR | |||
| Mevastatin (254) | Antihyperlipidemic | × | HMG-CoA | |||
| Bexarotene (296) | Antineoplastic | × | RXR | |||
| Fluphenazine⋅2HCl (97) | Antipsychotic | × | GPCRs | |||
| Calcifediol (220) | Vitamin/antirachitic | × | Vitamin D | |||
a
Compound numbers are given in parentheses. The previously established therapeutic class and targeted pathway are given for each agent. Target pathways are abbreviated as follows: GPCR, G protein-coupled receptors; S, sterol/hormone; COMT, catechol-O-methyl transferase; PDE, phosphodiesterase; IonC, ion channel; GCR, glucocorticoid receptor; ATR, angiotensin receptor; PPAR, peroxisome proliferator-activated receptor; TK, tyrosine kinase; HER, human epidermal growth factors receptor; HMG-CoA, hydroxymethylglutaryl-CoA reductase; and RXR, retinoid X receptor. × represents >80% inhibition of the intracellular growth. Pathogens are abbreviated as follows: Cb, C. burnetii; Lp, L. pneumophila; Ba, B. abortus; and Rc, R. conorii.