title: Identification of a novel class of quinoline-oxadiazole hybrids as anti-tuberculosis agents.
abstract: A series of novel quinoline-oxadiazole hybrid compounds was designed based on stepwise rational modification of the lead molecules reported previously, in order to enhance bioactivity and improve druglikeness. The hybrid compounds synthesized were screened for biological activity against Mycobacterium tuberculosis H37Rv and for cytotoxicity in HepG2 cell line. Several of the hits exhibited good to excellent anti-tuberculosis activity and selectivity, especially compounds 12m, 12o and 12p, showed minimum inhibitory concentration values<0.5μM and selectivity index>500. The results of this study open up a promising avenue that may lead to the discovery of a new class of anti-tuberculosis agents.
authors.affiliation: Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai 400019, India.
authors.forename: Puneet P
authors.initials: PP
authors.lastname: Jain
authors.affiliation: Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai 400019, India.
authors.forename: Mariam S
authors.initials: MS
authors.lastname: Degani
authors.affiliation: Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai 400019, India.
authors.forename: Archana
authors.initials: A
authors.lastname: Raju
authors.affiliation: Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai 400019, India.
authors.forename: Aarti
authors.initials: A
authors.lastname: Anantram
authors.affiliation: Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai 400019, India.
authors.forename: Madhav
authors.initials: M
authors.lastname: Seervi
authors.affiliation: Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai 400019, India.
authors.forename: Sadhana
authors.initials: S
authors.lastname: Sathaye
authors.affiliation: Radiation Medicine Centre, Tata Memorial Hospital, Parel, Mumbai 400012, India.
authors.forename: Muktikanta
authors.initials: M
authors.lastname: Ray
authors.affiliation: Radiation Medicine Centre, Tata Memorial Hospital, Parel, Mumbai 400012, India.
authors.forename: M G R
authors.initials: MGR
authors.lastname: Rajan
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D008862:Microsomes, Liver / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D010069:Oxadiazoles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011804:Quinolines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D014376:Tuberculosis / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents; D010069:Oxadiazoles; D011804:Quinolines; C037219:quinoline
keywords: Bedaquiline; Isosterism; Mycobacterium tuberculosis; Oxadiazole; Quinoline