NO donor hybrid compounds as multifunctional therapeutic agents

Abstract

Background : In the 1980s, nitric oxide (NO) was found to be a crucial signaling and regulating molecule with wide-ranging functions in the cardiovascular, nervous and immune systems, such as blood vessel relaxation, neurotransmission and pathogen suppression. Deficiency or dysfunction of NO, which may result from ageing and other etiological or pathological factors, is implicated in the initiation and progression of many diseases. Delivery of supplementary NO is thought to be an attractive therapeutic option to prevent disease progression; NO donor hybrid compounds are also suspected of being useful. Objectives : These bi-or multifunctional compounds contain an NO-releasing moiety linked to another well-established biologically active molecule mostly through some kind of spacer. Such hybrid compounds may perform as intact molecules or be metabolized, yielding two or even more parent pharmacophores in vivo and perhaps producing a synergic response. From the middle of the 1990s up to now, a considerable number of NO hybrid compounds have been synthesized and screened. The role of NO donor hybrid compounds has been extended from the initial inflammatory and cardiovascular diseases to gastrointestinal disorders, microbial infections, cancer, neurodegenerative diseases, sexual dysfunction, ocular hypertension and others. Method/conclusion : In this review, we introduce NO donor hybrid compounds, then focus on the corresponding relevant patents with regard to its various applications and, in conclusion, discuss the chances and drawbacks of this strategy in drug discovery.

Nitric Oxide (NO) and NO Synthases (NOS)-Based Targeted Therapy for Colon Cancer

“…NO donor-based therapy has been advanced from an NO donor alone towards the (1) co-administration of NO donors with other chemo-/radio-/immune-therapy; (2) hybridization of NO donors with gaseous transmitters, such as hydrogen sulfide (H 2 S) and carbon monoxide (CO); (3) combinational use of iNOS and COX inhibitors; and (4) application of drug delivery systems, such as nanotechnology, to deliver a high level of NO to the tumor sites. In this section, we review the advances of NO donor-based therapy in CRC made in the past decades and provide prospects [79][80][81][82][83].…”

Synthesis and Modeling Studies of Furoxan Coupled Spiro-Isoquinolino Piperidine Derivatives as NO Releasing PDE 5 Inhibitors

“…A considerable number of NO hybrid compounds have been synthesized and screened. The role of NO donor hybrid compounds has been extended from the initial inflammatory and cardiovascular diseases to gastrointestinal disorders, microbial infections, cancer, neurodegenerative diseases, sexual dysfunction, ocular hypertension, and others [42,43]. NO-hybridization of parental drugs such as aspirin [44], isoxazoline compounds (VGX-1027), and antiretroviral protease inhibitors has been largely studied and NO hybridization has been found to often improve and eventually extend the pharmacological properties of parental compounds in suppression of cancer and immunoinflammatory responses [45,46].…”