{"doi":"10.3390/molecules27092844","title":"Design, Synthesis and Biological Evaluation of N-phenylindole Derivatives as Pks13 Inhibitors againstMycobacterium tuberculosis","abstract":"Polyketide synthase 13 (Pks13), an essential enzyme for the survival of Mycobacterium tuberculosis (Mtb), is an attractive target for new anti-TB agents. In our previous work, we have identified 2-phenylindole derivatives against Mtb. The crystallography studies demonstrated that the two-position phenol was solvent-exposed in the Pks13-TE crystal structure and a crucial hydrogen bond was lost while introducing bulkier hydrophobic groups at indole N moieties. Thirty-six N-phenylindole derivatives were synthesized and evaluated for antitubercular activity using a structure-guided approach. The structure–activity relationship (SAR) studies resulted in the discovery of the potent Compounds 45 and 58 against Mtb H37Rv, with an MIC value of 0.0625 μg/mL and 0.125 μg/mL, respectively. The thermal stability analysis showed that they bind with high affinity to the Pks13-TE domain. Preliminary ADME evaluation showed that Compound 58 displayed modest human microsomal stability. This report further validates that targeting Pks13 is a valid strategy for the inhibition of Mtb and provides a novel scaffold for developing leading anti-TB compounds.","journal":"Molecules","year":2022,"id":261940,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9637,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":879671,"name":"Wei Zhang","orcid":"0000-0002-4840-8174","position":1,"is_corresponding":false},{"id":352337,"name":"Shichun Lun","orcid":null,"position":2,"is_corresponding":false},{"id":917189,"name":"Tongtong Zhu","orcid":"0000-0002-9481-8203","position":3,"is_corresponding":false},{"id":917190,"name":"Weijun Xu","orcid":"0000-0002-4162-5440","position":4,"is_corresponding":false},{"id":689348,"name":"Fan Yang","orcid":"0000-0002-0411-7391","position":5,"is_corresponding":false},{"id":543920,"name":"Jie Tang","orcid":"0000-0001-9864-7467","position":6,"is_corresponding":false},{"id":241544,"name":"William R. Bishai","orcid":"0000-0002-8734-4118","position":7,"is_corresponding":false},{"id":689349,"name":"Li-Fang Yu","orcid":"0000-0002-3250-6773","position":8,"is_corresponding":false},{"id":880272,"name":"Yan-Peng Cai","orcid":null,"position":0,"is_corresponding":true}],"reference_count":27,"raw_metadata":null,"created_at":"2026-07-19T00:26:20.717229Z","pmid":"35566191","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}