3.3.3. Pyridines

Piericidins feature a 4-pyridinol core linked with a variable methylated polyene side chain. The strain *Streptomyces iakyrus* SCSIO NS104, isolated from a mangrove sediment sample collected from the Pearl River estuary to the South China Sea, yielded four new piericidin analogues, iakyricidins A–D (**125**–**128**) [113]. Iakyricidins B–D (**126**–**128**) represent a new subgroup of piericidin with C-C cyclization and double bond rearrangements in the polyene side chain. In addition, oxidized side chain piericidin analogue iakyricidin A (**125**) displayed potent antiproliferative activity against human renal carcinoma cell lines ACHN

cell with an IC50 value of 20 nM. Compound **125** might be derived by oxidative cleavage between C-13 and C-14 of the precursor. In the plausible biosynthetic pathways of **126**–**128**, the most crucial step would be the yet-to-be-identified enzymatic C8-C12 cyclization from the co-occurrence precursor (Scheme 25).

**Scheme 25.** Proposed biosynthetic pathway for compounds **125**–**128** [113].

Chemical investigation of the endophytic fungus *Campylocarpon* sp. HDN13-307, obtained from the root of mangrove plant *Sonneratia caseolaris* led to the isolation of four new 4-hydroxy-2-pyridone alkaloids, namely campyridones A–D (**129**–**132**) [114] (Figure 35), which existed as two pairs of diastereoisomers, featuring an additional C ring between the decalin and pyridone units, represented new ring systems for this family of alkaloids. A plausible biosynthetic pathway for **129**–**132** is postulated with the co-occurrence ilicicolin H as a critical intermediate. Ilicicolin H is a typical 4-hydroxy-2-pyridone alkaloid which was considered to be biosynthesized via tetramic acids formed by hybridizing a polyketide unit to a tyrosine (Scheme 26). Compound **132** exhibited activity against Hela cells with IC50 values of 8.8 *μ*M.

**Figure 35.** Structures of compounds **129**–**132**.

**Scheme 26.** Proposed biosynthetic pathway for compounds **129**–**132** [114].
