Over a long period of time, humans have explored many natural resources looking for remedies of various ailments. Traditional medicines have played an intrinsic role in human life for thousands of years, with people depending on medicinal plants and their products as dietary supplements as well as using them therapeutically for treatment of chronic disorders, such as cancer, malaria, diabetes, arthritis, inflammation, and liver and cardiac disorders. However, plant resources are not sufficient for treatment of recently emerging diseases. In addition, the seasonal availability and other political factors put constrains on some rare plant species. The actual breakthrough in drug discovery came concurrently with the discovery of penicillin from Penicillium notatum in 1929. This discovery dramatically changed the research of natural products and positioned microbial natural products as one of the most important clues in drug discovery due to availability, variability, great biodiversity, unique structures, and the bioactivities produced. The number of commercially available therapeutically active compounds from microbial sources to date exceeds those discovered from other sources. In this review, we introduce a short history of microbial drug discovery as well as certain features and recent research approaches, specifying the microbial origin, their featured molecules, and the diversity of the producing species. Moreover, we discuss some bioactivities as well as new approaches and trends in research in this field.

Over the last decades, endophytic fungi represent a new source of pharmacologically active secondary metabolites based on the underlying assumption that they live symbiotically within their plant host. In the present study, a new endophytic fungus was isolated from Rauwolfia macrophylla, a medicinal plant from Cameroon. The fungus showed a highest homology to Curvularia sp. based on complete nucleotide sequence data generated from the internal transcribed spacer (ITS) of ribosomal DNA region. Large scale fermentation, working-up and separation of the strain extract using different chromatographic techniques afforded three bioactive compounds: 2'-deoxyribolactone (1), hexylitaconic acid (2) and ergosterol (3). The chemical structures of compounds 1–3 were confirmed by 1 and 2D NMR spectroscopy and mass spectrometry, and comparison with corresponding literature data. Biologically, the antimicrobial, antioxidant activities and the acetylcholinesterase inhibitory of the isolated compounds were studied.

The crystal structure and unambiguous absolute configuration of meleagrin (1) isolated from fungus Emericella dentata Nq45 is reported herein to first time on the bases of single crystal X-ray diffraction. Together with 1, haenamindole (2), isorugulosuvine (3), secalonic acid D (4), ergosterol (5) and cerebroside A (6) were obtained and their structures were determined by ESI MS and NMR data analysis. Diverse biological activity of meleagrin (1) was investigated. Compound 1 pronounced potent cytotoxicity against the human cervix carcinoma cell line KB-3-1 and its multidrug resistant sub-clone KB-V1 of IC₅₀ 3.07 and 6.07 µM, respectively, in comparison with the reference (+) – griseofulvin (IC₅₀ 19, 19.5 µM). Based on the antibiofilm activity, compound 1 displayed as well potent activity against Staphylococcus aureus with an MIC of 0.25 mg/mL. Isolation of the producing fungus and taxonomical characterization is stated as well.

Terretonin N (1), a new highly oxygenated and unique tetracyclic 6-hydroxymeroterpenoid, was isolated together with seven known compounds from the ethyl acetate extract of a solid-state fermented culture of Nocardiopsis sp. Their structures were elucidated by spectroscopic analysis. The structure and absolute configuration of 1 were unambiguously determined by X-ray crystallography. The isolation and taxonomic characterization of Nocardiopsis sp. is reported. The antimicrobial activity and cytotoxicity of the strain extract and compound 1 were studied using different microorganisms and a cervix carcinoma cell line, respectively.

• Isolation and characterization of five polyketides 1–5 from the marine endophytic Alternaria sp. LV52 derived from Cystoseira tamariscifolia. • The chemical structures of compounds 1–5 were identified by extensive 1D, 2D NMR, and HR mass measurements, and by comparison with literature data. • Isolation and taxonomic characterization of the producing fungus is intensively reported on the bases of morphological and genotypic analysis. • The antimicrobial of the produced extract and derived compounds were examined against a panel of test organisms. • Compounds 2 and 4 are potentially cytotoxic against human non-small cell lung (A549) and prostate (PC3) cancer cell lines.