| Summary: | <i>Combretum padoides</i> Engl. & Diels, <i>C. psidioides</i> Welv. and <i>C. zeyheri</i> Sond. are used for the treatment of infections and tuberculosis related symptoms in African traditional medicine. In order to verify these uses, extracts were screened for their growth inhibitory effects against <i>M. smegmatis</i> ATCC 14468. Ultra-high pressure liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC/QTOF-MS) and GC-MS were used to investigate the polyphenolic composition in the active extracts. The lowest minimum inhibitory concentration (MIC), 625 µg/mL, was shown by a methanol extract of the stem bark of <i>C. psidioides</i>. A butanol extract of <i>C. psidioides</i> gave large inhibition zone diameters (IZD 21 mm) and inhibited 84% of the mycobacterial growth at 312 µg/mL. Combretastatin B-2 and dihydrostilbene derivatives were present in the methanol extract of <i>C. psidioides</i>, whereas the butanol extract of this species contained punicalagin, corilagin, and sanguiin H-4. Methanol and butanol extracts of the stem bark of <i>C. padoides</i> gave large inhibition zone diameters (IZD 26.5 mm) and MIC values of 1250 and 2500 µg/mL, respectively. <i>C. padoides</i> contained an ellagitannin with a mass identical to punicalagin ([M-H]<sup>−</sup> 1083.0587) and a corilagin like derivative ([M-H]<sup>−</sup> 633.0750) as well as ellagic acid arabinoside and methyl ellagic acid xyloside. A butanol extract of the roots of <i>C. zeyheri</i> showed mild antimycobacterial activity and contained a gallotannin at <i>m</i>/<i>z</i> [M-H]<sup>−</sup> 647.0894 as the main compound along with punicalagin and three unknown ellagitannins at <i>m</i>/<i>z</i> [M-H]<sup>−</sup> 763.0788, 765.0566, and 817.4212. Our results indicate that the studied species of <i>Combretum</i> contain phenolic and polyphenolic compounds with possible potential as leads for antimycobacterial drugs or as adjuvants for conventional anti-TB drugs.
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