The screening results (Table 1) revealed that phloroglucinol (1) and phloracetophenones (2a, 2d–f) demonstrated weak inhibition of soybean 15-LOX, with values ranging between 16% and 24% at 100 μg/mL concentration. Intermediates 2c and 2g did not exhibit any anti-inflammatory activity against the enzyme. Meanwhile the geranylated compounds (3a, 3c, 3e–g) demonstrated moderate to excellent anti-inflammatory activities in a dose-dependent manner with IC50 ranging from 10.31 to 27.61 μM. The IC50 value of NDGA (reference compound), tHGA and its analogs with intermediates are shown in Table 1. It is noted that the IC50 value of tHGA (parent compound) was consistent with our previous study [17]. Interestingly, the three target compounds (3c, 3e and 3g) exhibited better soybean 15-LOX inhibition with improvement in activities ranging from approximately 30%–50%.