title: Synthesis and biological evaluation of tricyclic guanidine analogues of batzelladine K for antimalarial, antileishmanial, antibacterial, antifungal, and anti-HIV activities.
abstract: Fifty analogues of batzelladine K were synthesized and evaluated for in vitro antimalarial (Plasmodium falciparum), antileishmanial (Leishmania donovani), antimicrobial (panel of bacteria and fungi), antiviral (HIV-1) activities. Analogues 14h and 20l exhibited potential antimalarial activity against chloroquine-sensitive D6 strain with IC(50) 1.25 and 0.88 μM and chloroquine-resistant W2 strain with IC(50) 1.64 and 1.07 μM, respectively. Analogues 12c and 14c having nonyl substitution showed the most potent antileishmanial activity with IC(50) 2.39 and 2.78 μM and IC(90) 11.27 and 12.76 μM, respectively. Three analogues 12c, 14c, and 14i were the most active against various pathogenic bacteria and fungi with IC(50) < 3.02 μM and MIC/MBC/MFC <6 μM. Analogue 20l having pentyl and methyl substituents on tricycle showed promising activities against all pathogens. However, none was found active against HIV-1. Our study demonstrated that the tricyclic guanidine compounds provide new structural class for broad spectrum activity.
authors.affiliation: Department of Natural Products, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali, Punjab 160062, India.
authors.forename: Nafees
authors.initials: N
authors.lastname: Ahmed
authors.forename: Keyur G
authors.initials: KG
authors.lastname: Brahmbhatt
authors.forename: Shabana I
authors.initials: SI
authors.lastname: Khan
authors.forename: Melissa
authors.initials: M
authors.lastname: Jacob
authors.forename: Babu L
authors.initials: BL
authors.lastname: Tekwani
authors.forename: Sudeep
authors.initials: S
authors.lastname: Sabde
authors.forename: Debashis
authors.initials: D
authors.lastname: Mitra
authors.forename: Inder P
authors.initials: IP
authors.lastname: Singh
authors.forename: Ikhlas A
authors.initials: IA
authors.lastname: Khan
authors.forename: Kamlesh K
authors.initials: KK
authors.lastname: Bhutani
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001232:Aspergillus fumigatus / Q000187:drug effects; D002175:Candida / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D003455:Cryptococcus neoformans / Q000187:drug effects; D019791:Guanidine / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D006146:Guanidines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D015497:HIV-1 / Q000187:drug effects; D007893:Leishmania donovani / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects; D013329:Structure-Activity Relationship; D014709:Vero Cells
chemical_list: D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents; D000935:Antifungal Agents; D000962:Antimalarials; D006146:Guanidines; C583449:batzelladine K; D019791:Guanidine