Antitumor Agents. 166. Synthesis and Biological Evaluation of 5,6,7,8-Substituted-2-phenylthiochromen-4-ones

Hk, Wang; Kf, Bastow; Lm, Cosentino; Kh, Lee

doi:10.1021/jm960008c

Cited by 77 publications

(29 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, it is conceivable that ciprofloxacin and trovafloxacin exert their inhibitory effects on HIV replication via an inhibition of TNF-α synthesis. However, it can not be ruled out that FQs and compounds with a quinolone-like structure exhibit anti-HIV activity by targeting viral reverse transcriptase and Tat [122][123][124][125].…”

Section: Possible Contributions Of the Immunomodulatory Effects Of Fqmentioning

confidence: 99%

Immunomodulatory Activities of Fluoroquinolones

2005

View full text Add to dashboard Cite

A review of published data on the in vitro, ex vivo, in vivo and clinical effects of fluoroquinolones on the synthesis of cytokines is provided. Fluoroquinolones (FQs) were found to affect both cellular and humoral immunity. In general, FQs exert their modulating effects only when used together with a co-stimulant. The in vitro studies generated heterogeneous data because of inhomogeneous effects triggered by different types of co-stimulants and differing responses of various cell lines on the stimuli. However, there is the general trend that FQs decrease the synthesis of pro-inflammatory cytokines. Studies in experimental animals generated homogenous data. All the FQs studied exerted significant clinical effects by attenuating cytokine responses in vivo. The FQs were found to be effective in vivo either in infections caused by organisms against which these are inactive or when dosed suboptimally, so that serum levels were lower than the susceptibilities of the causative pathogens. These in vivo effects were correlated with a significant decrease in pro-inflammatory cytokines like Il-1 and TNF. In addition, FQs were found to upregulate hematopoiesis. These immunomodulatory effects can be attributed in particular to those FQs with a cyclopropyl-moiety at the position N1 of the quinolone core structure, i. e. ciprofloxacin, moxifloxacin, grepafloxacin, sparfloxacin. The immunomodulatory effects of the FQs are due to their effects on intracellular cyclic AMP and phosphodiesterases, on transcription factors such as NF-kappa B, activator protein 1 and a triggering effect on the eucaryotic equivalent of bacterial SOS response. All these studies indicate that FQs exert immunomodulatory activities in particular in latent or chronic infections.

show abstract

Section: Possible Contributions Of the Immunomodulatory Effects Of Fqmentioning

confidence: 99%

Immunomodulatory Activities of Fluoroquinolones

2005

View full text Add to dashboard Cite

show abstract

“…97 Replacing the ether oxygen of 128 with sulfur in a series of analogous 2-phenylthiochromen-4-ones did not achieve better activity. 98,99 Lawinal (129), a flavonoid from Desmos spp., demonstrated anti-HIV activity (EC 50 ; ¼ 7.72 mM, TI ¼ 45). However, the most potent flavonoid-related compound was the chalcone 2-methoxy-3-methyl-4,6-dihydroxy-5-(3 0 -hydroxy)cinnamoylbenzaldehyde (130) (EC 50 ¼ 0.067 mM, TI ¼ 489).…”

Section: Flavonoidsmentioning

confidence: 99%

New developments in natural products‐based anti‐AIDS research

Morris‐Natschke

Lee

2006

Medicinal Research Reviews

Self Cite

View full text Add to dashboard Cite

This review discusses anti-HIV natural products from several compound classes, including terpenoids, coumarins, alkaloids, polyphenols, tannins, and flavonoids. Natural products can provide novel anti-AIDS chemotherapeutic leads that are structurally unique or have new mechanisms of action. The drug discovery and development process proceeds from bioactivity-directed isolation and identification of a promising lead natural product, followed by rational design-based structural modification and structure-activity relationship analyses to optimize the lead compound as a drug candidate. This process is notably exemplified by the discovery of the modified betulinic acid derivative, DSB [PA-457], which is currently in Phase II clinical trial and is the first-in-class HIV maturation inhibitor (MI).

show abstract

“…4-Quinolone derivatives have attracted attention owing to their use as antibacterials, e.g. ciprofloxacin and other 6-fluoroquinolones [17,18], they are active against a great variety of infections including anthrax, and have also shown to be antitumor [19][20][21] and antimitotic [22] agents. Some other protection derivatives are particularly important because of their antimalaric activity [23,24].…”

Section: Introductionmentioning

confidence: 99%