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Sains Malaysiana 55(8)(2026): 1324-1336
http://doi.org/10.17576/jsm-2026-5508-08
Harnessing Rubiaceae Plant Endophytic Fungi: A Comprehensive
Review of Novel Antimicrobial Compounds for Drug Discovery
(Memanfaatkan Kulat Endofitik Tumbuhan Rubiaceae: Ulasan Komprehensif Sebatian Antimikrob Baharu untuk Penemuan Ubat)
INHERNI MARTI ABNA1,2,*, MARLIA SINGGIH WIBOWO1,
IRDA FIDRIANNY1 & ANDRIA AGUSTA3
1School of Pharmacy, Bandung Institute of Technology, Jl.
Ganesa 10, Bandung, West Java 40132, Indonesia
2Pharmacy Study Program, Faculty of Health Sciences,
Universitas Esa Unggul, Jl. Arjuna Utara No.9, Duri
Kepa, Kebon Jeruk Sub-District, West Jakarta City, Special Capital Region of Jakarta 11510,
Indonesia
3Research Center for Pharmaceutical Ingredients and
Traditional Medicine, National Research and Innovation Agency, Jl. Raya
Jakarta-Bogor Km. 46, Cibinong, West Java 16915, Indonesia
Received:
26 November 2025/Accepted: 5 August 2026
Abstract
Antimicrobial resistance (AMR)
continues to threaten the effectiveness of existing therapies, driving the
urgent search for novel therapeutic leads from nature. Rubiaceae plant-associated endophytic fungi are increasingly recognized as valuable
producers of structurally diverse secondary metabolites with antibacterial,
antifungal, and antimycobacterial activities. Unlike previous reviews that
primarily focus on bioactive compounds, this narrative-critical review
integrates ecological factors influencing endophytic diversity with advanced
strategies to awaken cryptic biosynthetic pathways. We systematically evaluate
approaches including One Strain-Many Compounds (OSMAC), co-culture, chemical
and epigenetic elicitation, genome-guided discovery, and heterologous
expression. Furthermore, this review critically analyzes pharmacological
metrics, specifically minimum inhibitory concentration (MIC), cytotoxicity,
Selectivity Index (SI), mechanisms of action, and the potential of fungal
metabolites as antibiotic adjuvants. Current evidence suggests that the
clinical development of these natural products is constrained by methodological
inconsistencies, a lack of animal model testing, insufficient pharmacokinetic
profiling, and large-scale manufacturing hurdles. Future progress in drug
discovery will heavily depend on adopting standardized evaluation criteria and
comprehensive pharmacological screening to successfully transform these endophytic
metabolites into viable clinical candidates.
Keywords: Antimicrobial secondary
metabolites; drug discovery; endophytic fungi; OSMAC; Rubiaceae;
selectivity index
Abstrak
Kerintangan antimikrob (AMR) terus mengancam keberkesanan terapi sedia ada, sekali gus mendorong pencarian segera untuk terapeutik baharu daripada alam semula jadi. Kulat endofit yang berkaitan dengan tumbuhan famili Rubiaceae semakin dikenali sebagai pengeluar pelbagai metabolit sekunder yang memiliki aktiviti antibakteria, antikulat dan antimikobakteria. Tidak seperti ulasan terdahulu yang sebahagian besarnya tertumpu kepada sebatian bioaktif, ulasan ini menggabungkan faktor ekologi yang mempengaruhi kepelbagaian endofit dengan strategi lanjutan untuk meningkatkan laluan biosintetik yang masih samar. Kami menilai pelbagai pendekatan secara sistematik termasuk Satu Strain-Banyak Sebatian (OSMAC), kultur bersama, elisitasi kimia dan epigenetik, penemuan berpandukan genom dan pengekspresan heterolog. Tambahan pula, ulasan ini menganalisis secara kritis metrik farmakologi, khususnya kepekatan perencatan minimum (MIC), kesitotoksikan, Indeks Kepilihan (SI), mekanisme tindakan dan potensi metabolit kulat sebagai adjuvan antibiotik. Bukti semasa mencadangkan bahawa pembangunan klinikal produk semula jadi ini masih dikekang oleh ketidakseragaman metodologi, kekurangan ujian model haiwan, pemprofilan farmakokinetik yang tidak mencukupi dan halangan pembuatan berskala besar. Kemajuan pada masa hadapan dalam penemuan ubat akan sangat bergantung kepada penerapan kriteria penilaian piawai dan penyaringan farmakologi yang komprehensif untuk berjaya mentransformasikan metabolit endofit ini menjadi calon klinikal yang berdaya maju.
Kata kunci: Indeks keselektifan; kulat endofit; metabolit sekunder antimikrob; OSMAC; penemuan ubat; Rubiaceae
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*Corresponding author, email: inherni.martiabna@esaunggul.ac.id
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