Article Phytochemical Analysis of Bangladeshi Medicinal Plants Led to the Isolation of Anti-Staphylococcal Compounds Holly Siddique 1,2,* and Mukhleshur Rahman 3 1 Department of Clinical and Pharmaceutical Science, School of Life and Medical Science, University of Hertfordshire, College Lane, Hatfield AL10 9AB, UK 2 Royal Botanic Gardens Kew, Kew Green, Richmond, Surrey TW9 3AE, UK 3 Medicines Research Group, School of Health, Sports and Bioscience, University of East London, Stratford Campus, Water Lane, London E15 4LZ, UK * Correspondence: h.siddique@herts.ac.uk Received: 20 June 2024; Revised: 26 August 2024; Accepted: 12 September 2024; Published: 24 September 2024 Abstract: Antibacterial resistance is a major threat to global health. Due to its new resistance mechanisms, it is spreading and emerging widely, thereby threatening the treatment of common infectious diseases. Ancient history and ethnopharmacological studies highlighted the importance of natural sources in treating resistance infections. This study involved bioassay-directed phytochemical investigation on Bangladeshi medicinal plants selected by an ethnopharmacological survey to explore antibacterial compounds against Methicillin resistance Staphylococcus aureus (MRSA). In 2016, an ethnopharmacological survey conducted in Bangladesh led to the recommendation of 71 medicinal plants by 127 respondents (71 Ayurvedic/Unani practitioners, 21 Ayurvedic patients and 35 local inhabitants) for the treatment of infectious diseases. Based on the literature review, data analysis of the ethnopharmacological survey and ease of availability of the plants, 18 plants were initially selected and collected from Bangladesh. After the initial antibacterial screening of 18 plants, five plants with Minimum Inhibitory Concentration (MIC) of 32–512 µg/mL were chosen based on potential antibacterial activity. These are (Zingiber montanum, Uraria picta, Diospyros malabarica, Cynometra ramiflora, Swertia chirayita. Extensive phytochemical work using different chromatographic and spectroscopic techniques on five Bangladeshi medicinal plants led to the isolation and identification of 24 compounds. Eight terpenes (zerumbol (3), zerumbone (4), buddledone A (5), germacrone (6), furanodienone (7), (−) borneol (1), camphor (2) and 8(17), 12-labdadiene-15, 16-dial) (8) were isolated from Zingiber montanum with the MIC (32– >128 µg/mL). Eugenol (14) and steroids were isolated from Uraria picta (MIC 64– >128 µg/mL). Lupane-type triterpenoids (Lupeol (20), betulin (21), betulinaldehyde (23), betulone (24) and messagenin (22) were isolated and identified from Diospyros malabarica with the MIC (64– >128 µg/mL), while pentacyclic triterpene (glutinol (10), glutinone (11)), simple phenolic (ethyl 4-ethoxybenzoate (9)) and steroids were isolated from Cynometra ramiflora with MIC (64– >128 µg/mL). A series of xanthones (swerchirin (16), swertiaperenin (17), bellidifolin (18) and decussatin (19)) were identified from Swertia chirayita with MIC (>128 µg/mL). 4-ethoxybenzoate (9) and messagenin (22) were identified as new natural compounds among these compounds. In terms of activity, 8(17), 12-labdadiene-15, 16-dial (8) (32 µg/mL against ATCC 5941) and zerumbol (3) (32 µg/mL against EMRSA 15) exhibited potential antibacterial activity. Phytochemical discoveries of Bangladeshi medicinal plants gave a new dimension to exploring anti-staphylococcal compounds.