Synthesis of Dithiolopyrrolone Derivatives and Their Leukocyte-Increasing Activities

Abstract

In search of new antileukopenia agents, twenty dithiolopyrrolone derivatives were synthesized and evaluated for their leukocyte-increasing activities in normal mice. Among the synthesized compounds 4-23, compounds 5 and 6 showed significant leukocyte-increasing activity ( p < 0.01), and compounds 4, 9 and 16 had a moderate effect ( p < 0.05). Compound 5 also displayed stronger leukocyte-increasing activity than that of the positive recombinant human granulocyte colony stimulating factor (rhG-CSF). Above all, compound 5 would be a potential antileukopenia agent which deserved further research.

Discovery of novel N‐aryl pyrrothine derivatives as bacterial RNA polymerase inhibitors

“…The synthesis procedures for N ‐aryl pyrrothine derivatives are shown in Scheme 1, following the synthesis routes on previous reports with minor modifications (Li, Wever, et al, 2014; Li, Sun, et al, 2014; Tan et al., 2013). The starting material of compound 1 was obtained according to previous procedure (Tan et al., 2013).…”

“…Dithiolopyrrolones are a class of antibiotics that possess the unique pyrrolinonodithiole (4 H ‐ [1,2] dithiolo [4,3‐ b ] pyrrol‐5‐one) skeleton (Qin, Huang, Yu, & Deng, 2013). Currently, there are approximately 30 naturally occurring dithiolopyrrolone derivatives identified, including thiolutin, holomycin, aureothricin, xenorhabdin I, and thiomarinols (Figure 1) (Gao et al., 2014; Li, Wever, Walsh, & Bower, 2014; Li, Sun, Wang, & Tan, 2014; Maffioli et al., 2017). These derivatives belong to N ‐methyl, N ‐acyl pyrrothine (thiolutin type), N ‐acyl pyrrothine (holomycin type), and thiomarinols.…”

“…Natural dithiolopyrrolones exhibit relatively broad‐spectrum antibiotic activity against many Gram‐positive and Gram‐negative bacteria (Qin et al., 2013). In recent years, N ‐aryl pyrrothine derivatives have been reported to have anticancer (Li et al., 2007) and anti‐leukopenia activity (Li, Wever, et al, 2014; Li, Sun, et al, 2014; Tan et al., 2013).…”

“…The “switch region” located at the base of the clamp serves as a hinge that facilitates the clamp swinging between the open and closed state (Irschik, Gerth, Hofle, Kohl, & Reichenbach, 1983). The switch region is distinct from the rifamycins binding site on RNAP and is highly conserved in Gram‐positive and Gram‐negative bacteria (Li, Wever, et al, 2014; Li, Sun, et al, 2014). Myxopyronins, corallopyronins, and ripostatins target the switch region of the bacterial RNAP and prevent extension of RNA during transcription initiation by restraining the entry of the promoter DNA, which interacts with RNAP (Figure 1) (Ho, Husdson, Das, Arnold, & Ebright, 2009; Mukhopadhyay et al., 2008).…”

Bacterial pathogens: threat or treat (a review on bioactive natural products from bacterial pathogens)

“…[194][195][196][197][198][199] N-Aryl DTP analogues have been shown antitumor activity 198 and antileukopenia activity. 194,197 N-Aryl DTP with 2,4-dimethoxyphenyl moiety displayed potent antibacterial activity against clinical isolates of MRSA, RRSA, vancomycin-resistant S. aureus (VRSA), and moderately penicillin-resistant S. pneumoniae (MPRSP) with MIC values in the range of 0.125-2 mg mL À1 comparable to the antibiotic rifampin. 195 Previous works also showed that the biosynthetic pathway of DTPs is susceptible to be manipulated by feeding different organic acids or fatty acids to the cultures to modify the lateral acyl chain.…”