Rapid diagnosis of mycobacterium tuberculosis with electrical impedance spectroscopy in suspensions using interdigitated microelectrode

A Mycobacterium tuberculosis (MTB) bacilli are still widely spreading and have to be diagnosed fast and efficiently. Therefore, a new simple and rapid method was proposed to detect MTB by the impedance properties of MTB suspensions using interdigitated microelectrodes. As a result, MTB suspensions in deionized (DI) water with different cell concentrations generated different electrical impedance spectral responses. Whereas MTB suspensions in 0.9 wt. % NaCl solution did not produce any significant differences in the impedance spectra in response to different cell concentrations. In DI water suspensions, the impedance at 1 kHz decreased with increasing cell concentrations. The impedance of MTB suspension in DI water has been discussed; it was found to be resulted from the cell wall charges and release of ions from the cells. There was a linear relationship between the impedance and logarithmic value of the cell concentration in the cell concentration range of 10² to 10⁸ cfu/mL, which can be expressed by the regression equation of Z (kΩ) =–456lnN (cfu/mL) + 9717 with R² = 0.99. Detection limit was calculated as 10⁴ cfu/mL, which is comparable with many label-free immunosensors for detecting pathogenic bacteria reported in the literature. This work demonstrated that MTB concentration can be determined through measuring the impedance of MTB suspensions in DI water. This new detection mechanism can be an alternative for current impedance methods available for detecting bacterial cells.     

Synthesis of Ethylene Tethered Isatin‐Coumarin Hybrids and Evaluation of Their in vitro Antimycobacterial Activities

A series of novel isatin‐coumarin derivatives tethered through ethylene were designed, synthesized, and evaluated for their in vitro antimycobacterial activities against Mycobacterium tuberculosis (MTB) H37Rv and multidrug‐resistant tuberculosis (MDR‐TB). All hybrids exhibited potential antimycobacterial activities against MTB H37Rv and MDR‐TB with minimum inhibitory concentration (MIC) ranging from 32 to 256 μg/mL. In particular, the hybrid 4h (MIC: 50 and 32 μg/mL) was most active against MTB H₃₇Rv and MDR‐TB strains, which was 2 and >4 folds more potent than the first‐line antitubercular agents rifampicin (MIC: 64 μg/mL) and isoniazid (MIC: >128 μg/mL) against MDR‐TB, warrant further optimization.     

Design,Synthesis and In Vitro Antitubercular Evaluation of Isatin‐ciprofloxacin Hybrids with Hydrogen Bonding Capacity

A series of novel isatin‐ciprofloxacin hybrids inhaling oxime, semicarbazone, and thiosemicarbazone groups with hydrogen bonding capacity were designed, synthesized, and evaluated for their in vitro antitubercular activities against Mycobacterium tuberculosis (MTB) H37Rv and multidrug‐resistant‐TB (MDR‐TB). All hybrids endowed with potential activities against the tested MTB H37Rv and MDR‐TB strains with minimum inhibitory concentration (MIC) in a range of 0.20 to 128 μg/mL. In particular, the most active hybrid 5e (MIC: 0.20 and 0.5 μg/mL) was four and two times more active than the parent ciprofloxacin (MIC: 0.78 μg/mL) and rifampicin (MIC: 0.39 μg/mL) against MTB H37Rv, and 4–>256 times more potent than the three references ciprofloxacin (MIC: 2.0 μg/mL), rifampicin (MIC: 32 μg/mL), and isoniazid (>128 μg/mL) against MDR‐TB. Thus, this kind of hybrids holds great promise as future anti‐TB agents against both drug‐sensitive and drug‐resistant MTB strains infection.     

Tetraethylene Glycol Tethered Heteronuclear Bis‐isatin Derivatives: Design,Synthesis, and In Vitro Anti‐mycobacterial Activities

A series of novel tetraethylene glycol tethered heteronuclear bis‐isatin derivatives 7a – l were designed, synthesized, and evaluated for their in vitro anti‐mycobacterial activities against Mycobacterium tuberculosis (MTB) H37Rv and multidrug‐resistant TB (MDR‐TB) as well as cytotoxicity in VERO cell line. All hybrids exhibited potential anti‐mycobacterial activities against MTB H37Rv and MDR‐TB, and acceptable cytotoxicity. Among them, the heteronuclear bis‐isatin 7l [minimum inhibitory concentration (MIC): 16 and 16 μg/mL] was found to be most active against MTB H37Rv and MDR‐TB strains, which was 2‐fold and >8‐fold, respectively, more potent than were the first‐line anti‐tubercular agents rifampicin (MIC: 32 μg/mL) and isoniazid (MIC: >128 μg/mL) against MDR‐TB, also demonstrated acceptable cytotoxicity profile (CC₅₀: 62.5 μg/mL), could act as a starting point for further optimization.     

Design,Synthesis, and Antimycobacterial Activities of Diethylene Glycol Tethered Moxifloxacin–Isatin Hybrids

A new class of diethylene glycol tethered moxifloxacin–isatin hybrids 5a–l was designed, synthesized, and evaluated for their in vitro antimycobacterial activity against Mycobacterium tuberculosis (MTB) H37Rv and multidrug‐resistant tuberculosis (MDR‐TB) strains. Our results showed that all hybrids with higher lipophilicity than the parent moxifloxacin exhibited promising activity against the tested strains with minimum inhibitory concentration (MIC) in a range of 0.2–16 μg/mL. In particular, hybrid 5h (MIC: 0.20 and 0.5 μg/mL), which was found to be most active against MTB H37Rv and MDR‐TB, was twofold more potent than isoniazid (MIC: 0.39 μg/mL) against MTB H37Rv and ≥64‐fold more active than isoniazid and rifampicin (MIC: >128 and 32 μg/mL, respectively) against MDR‐TB.     

Identification of glucosyl-3-phosphoglycerate phosphatase as a novel drug target against resistant strain of Mycobacterium tuberculosis (XDR1219) by using comparative metabolic pathway approach

Tuberculosis (TB) is a major global health challenge. It has been afflicting human for thousands of years and is still severely affecting a huge population. The etiological agent of the disease is Mycobacterium tuberculosis (MTB) that survives in the human host in latent, dormant, and non-replicative state by evading the immune system. It is one of the leading causes of infection related death worldwide. The situation is exacerbated by the massive increase in the resistant strains such as multi-drug resistant TB (MDR-TB) and extensive drug-resistant TB (XDR-TB). The resistance is as severe that it resulted in failure of the current chemotherapy regimens (i.e. anti-tubercular drugs). It is therefore imperative to discover the new anti-tuberculosis drug targets and their potential inhibitors. Current study has made the use of in silico approaches to perform the comparative metabolic pathway analysis of the MTBXDR1219 with the host i.e. H. sapiens. We identified several metabolic pathways which are unique to pathogen only. By performing subtractive genomic analysis 05 proteins as potential drug target are retrieved. This study suggested that the identified proteins are essential for the bacterial survival and non-homolog to the host proteins. Furthermore, we selected glucosyl-3-phosoglycerate phosphatase (GpgP, EC 5.4.2.1) out of the 05 proteins for molecular docking analysis and virtual screening. The protein is involved in the biosynthesis of methylglucose lipopolysaccharides (MGLPs) which regulate the biosynthesis of mycolic acid. Mycolic acid is the building block of the unique cell wall of the MTB which is responsible for the resistance and pathogenicity. A relatively larger library consisting of 10,431 compounds was screened using AutoDock Vina to predict the binding modes and to rank the potential inhibitors. No potent inhibitor against MTB GpgP has been reported yet, therefore ranking of compounds is performed by making a comparison with the substrate i.e. glucosyl-3-phosphoglycerate. The obtained results provide the understanding of underlying mechanism of interactions of ligands with protein. Follow up study will include the study of the Protein-Protein Interactions (PPIs), and to propose the potential inhibitors against them.     

Design,Synthesis, and In Vitro Anti‐mycobacterial Activities of Propylene‐Tethered Gatifloxacin‐Isatin Hybrids

A series of propylene‐tethered mono‐/bis‐isatin‐gatifloxacin hybrids 3a–f and 4a–f were designed, synthesized, and evaluated for their in vitro anti‐mycobacterial activities against Mycobacterium tuberculosis (MTB) H37Rv and multidrug‐resistant tuberculosis (MDR‐TB) as well as cytotoxicity against VERO cell line. The results indicated that all hybrids exhibited promising anti‐mycobacterial activities against MTB H37Rv and MDR‐TB with MIC ranging from 0.25 to 16 μg/mL. In particular, the mono‐isatin‐gatifloxacin hybrid 3e (MIC: 0.25 and 0.25 μg/mL) was found to be most active against MTB H₃₇Rv and MDR‐TB strains, which was twofold more active than the parent gatifloxacin (MIC: 0.5 μg/mL) and comparable with rifampicin ( RIF ) (MIC: 0.25 μg/mL) against MTB H₃₇Rv, and 4‐ > 512 times more potent than the three references gatifloxacin (MIC: 1.0 μg/mL), RIF (MIC: 64 μg/mL), and isoniazid (>128 μg/mL) against MDR‐TB, could act as a starting point for further optimization.     

Design,Synthesis, and in vitro Antimycobacterial Activity of Propylene‐tethered Isatin Dimmers

A set of propylene‐tethered isatin dimmers 2a–i was synthesized via click chemistry and screened for their in vitro antimycobacterial activities against Mycobacterium tuberculosis (MTB) H₃₇Rv and multidrug‐resistant TB. In spite of all dimmers (minimum inhibitory concentration: 25– > 128 μg/mL) only exhibited weak to moderate activities against the tested MTB H₃₇Rv and multidrug‐resistant TB, the structure–activity relationship was enriched and the results warrant further development of the anti‐TB properties of this kind of dimmers.     

1H‐1,2,3‐triazole‐tethered 8‐OMe Ciprofloxacin and Isatin Hybrids: Design,Synthesis and in vitro Anti‐mycobacterial Activities

A new class of 1H ‐1,2,3‐triazole‐tethered 8‐OMe ciprofloxacin (8‐OMe CPFX) isatin hybrids 5a–l was designed, synthesized and screened for their in vitro anti‐mycobacterial activities against Mycobacterium tuberculosis H₃₇Rv and multi‐drug‐resistant tuberculosis (MDR‐TB). All targets (minimum inhibitory concentration (MIC): 0.20–8.0 μg/mL) exhibited promising inhibitory activity against MTB H₃₇Rv and MDR‐TB. Among them, conjugate 5h (MIC: 0.20 μg/mL), was 2–16 times more potent in vitro than the references CPFX (MIC: 3.12 μg/mL), 8‐OMe CPFX (MIC: 1.56 μg/mL) and RIF (MIC: 0.39 μg/mL) against MTB H₃₇Rv. The most potent hybrid 5l (MIC: 0.25 μg/mL) was 8–256 times more active than the three references (MIC: 2.0–64 μg/mL) against MDR‐TB. Both of them warrant further investigations.     

Isatin‐(thio)semicarbazide/oxime‐1H‐1,2,3‐triazole‐coumarin Hybrids: Design,Synthesis, and in vitro Anti‐mycobacterial Evaluation

Isatin and coumarin derivatives with potential anti‐tubercular activity, while (thio)semicarbazide/oxime and 1H‐1,2,3‐triazole moieties exhibited favorable properties such as hydrogen bonding and/or metal chelation capability, so integration of the four pharmacophores into one molecule may provide more effective anti‐tubercular candidates. Based on the consideration earlier, 12 isatin‐(thio)semicarbazide/oxime‐1H‐1,2,3‐triazole‐coumarin hybrids 8a–l were designed, synthesized, and evaluated for their in vitro anti‐mycobacterial activities against M. tuberculosis (MTB) H₃₇Rv and MDR‐TB. The results showed that all the hybrids (MIC: 50–>200 μg/mL) exhibited weak to moderate inhibitory activity against MTB H₃₇Rv and MDR‐TB, which were far less potent than the references isoniazid (MIC: 0.05 μg/mL) and rifampicin (MIC: 0.39 μg/mL) against MTB H₃₇Rv. The most active hybrid 8h (MIC: 50 μg/mL) was comparable with rifampicin (MIC: 32 μg/mL) and more active than isoniazid (MIC: >128 μg/mL) against MDR‐TB, could be act as a lead for further optimization. Moreover, the enriched structure–activity relationship paved the way to the further rational development of this kind of hybrids.     

Gatifloxacin–Isatin Hybrids and Their Antimycobacterial Activities

We report herein the design, synthesis, and antimycobacterial activity of a series of diethylene glycol tethered gatifloxacin–isatin hybrids 5a – o in this paper. Results revealed that all hybrids showed promising activity against both drug‐sensitive and multidrug‐resistant Mycobacterium tuberculosis strains with minimum inhibitory concentration (MIC) in a range of 1–128 μg/mL. Particularly, hybrid 5j with low cytotoxicity in VERO cell line was comparable with the parent gatifloxacin (MIC: 0.78 and 1 μg/mL) against MTB H37Rv and MDR‐TB strains, and ≥32‐fold more potent than isoniazid and rifampicin (MIC: >128 and 32 μg/mL, respectively) against MDR‐TB, suggesting it may serve as a new and promising candidate for further study.     

Design,Synthesis and in vitro Antimycobacterial Activities of Isatin‐1,2,3‐triazole‐moxifloxacin Hybrids

A new class of isatin‐1,2,3‐triazole‐moxifloxacin ( MXFX ) hybrids 5a–j was designed, synthesized, and screened for their in vitro antimycobacterial activities against Mycobacterium tuberculosis H₃₇Rv and MDR‐TB. All the synthesized hybrids (MIC: 0.10–0.78 μg/mL) exhibited excellent activities against MTB H₃₇Rv and MDR‐TB, in spite of none of them were more potent than the parent MXFX (MIC: 0.10 and 0.12 μg/mL). Against MTB H₃₇Rv, the most active 5f (MIC: 0.10 μg/mL) was comparable with MXFX and 4 times more potent than RIF (MIC: 0.39 μg/mL). Against MDR‐TB, all hybrids were more active than RIF (MIC: 32 μg/mL) and INH (MIC: >128 μg/mL). In particular, hybrid 5e (MIC: 0.10 μg/mL) was comparable with MXFX and 256 and >1,024 times more potent than RIF and INH . Both conjugates 5e and 5f warrant further investigations.     

Design,Synthesis and In Vitro Anti‐mycobacterial Activities of 8‐OMe Ciprofloxacin‐1H‐1,2,3‐triazole‐isatin‐(thio) Semicarbazide/Oxime Hybrids

A series of novel 8‐OMe ciprofloxacin (8‐OMe CPFX)‐1H‐1,2,3‐triazole‐isatin‐(thio) semicarbazide/oxime hybrids 6a – l with the capacity to form hydrogen bond were designed, synthesized, and evaluated for their in vitro anti‐mycobacterial activities against Mycobacterium tuberculosis (MTB) H₃₇Rv and MDR‐TB as well as cytotoxicity. All the synthesized hybrids (MIC: 0.39–16 μg/mL) exhibited excellent activities against MTB H₃₇Rv and MDR‐TB, and the majority of them were more potent than the parent 8‐OMe CPFX (MIC: 1.56 and 2.0 μg/mL, respectively). In particular, the most active conjugate 6h (MIC: 0.39 and 1.0 μg/mL, respectively) was two to eight times more potent in vitro than the references CPFX (MIC: 3.12 and 4.0 μg/mL, respectively) and 8‐OMe CPFX against the tested strains and was comparable with or 64‐folds more potent than RIF (MIC: 0.39 and 64 μg/mL, respectively) against MTB H₃₇Rv and MDR‐TB, respectively. In addition, all conjugates (CC₅₀: 16–64 μg/mL) showed acceptable cytotoxicity, although most of them were more toxic than the parent (CC₅₀: 64 μg/mL) in VERO cell line.     

Quinoline Derivatives with Potential Activity Against Multidrug‐resistant Tuberculosis

Tuberculosis (TB), which affects primarily the lungs (pulmonary TB) apart from other vital organs, is a life‐threatening chronic deadliest infectious disease caused by members of Mycobacterium tuberculosis (MTB) complex and mainly by MTB itself. The emergence of MTB new virulent forms that are resistant to some or all first‐line and second‐line anti‐TB agents, including multidrug‐resistant (MDR), extensively drug‐resistant, and totally drug‐resistant strains has further aggravated the spread of this disease and was increased up to an alarming level in the recent decades. More than ever, it is imperative to develop novel, high effective, and fast acting anti‐TB drugs to prevent the spread of TB, particularly in its hard‐to‐kill MDR‐TB, extensively drug‐resistant‐TB, and totally drug‐resistant‐TB strains. In recent years, numerous compounds have been synthesized for this purpose, but only a handful of compounds have entered human trials after the discovery of rifampicin, reflecting the inherent difficulties of developing new anti‐TB agents. Despite of bedaquiline and delamanid have received approval from many countries for treatment of MDR‐TB infected patients, both drugs are associated with serious side effects and are only recommended for those MDR‐TB patients without other treatment options. All these aforementioned facts make it an urgent need to develop novel drugs. Quinoline‐based derivatives including quinolones ex biological activities, and some of them displayed excellent in vitro and in vivo activities against MDR‐TB. This review outlines the recent developments of quinoline‐based derivatives with potential activity against MDR‐TB as well as the structure–activity relationship.     

Immunosensor towards low-cost, rapid diagnosis of tuberculosis

A rapid, accurate tuberculosis diagnostic tool that is compatible with the needs of tuberculosis-endemic settings is a long-sought goal. An immunofluorescence microtip sensor is described that detects Mycobacterium tuberculosis complex cells in sputum in 25 minutes. Concentration mechanisms based on flow circulation and electric field are combined at different scales to concentrate target bacteria in 1 mL samples onto the surfaces of microscale tips. Specificity is conferred by genus-specific antibodies on the microtip surface. Immunofluorescence is then used to detect the captured cells on the microtip. The detection limit in sputum is 200 CFU mL(-1) with a success rate of 96%, which is comparable to PCR.     

Analysis of fatty acids in sputum from patients with pulmonary tuberculosis using gas chromatography–mass spectrometry preceded by solid-phase microextraction and post-derivatization on the fiber

A method based on solid-phase microextraction (SPME) and post-derivatization on the fiber coupled to gas chromatography–mass spectrometry (GC–MS) was developed for the analysis of fatty acids in sputum from patients with pulmonary tuberculosis. The sputum specimens were digested, hydrolyzed, extracted, derivertized, injected and analyzed without cultivation or isolation of the microorganism. Under optimized conditions, the relative standard deviations (RSD, n = 5) for all analytes were below 17% and the limits of detection varied from 1.68 (C_24:0) to 150.4 μg L⁻¹ (C_12:0). Good linearity was observed for all the fatty acids studied except for C_12:0 within a wide concentration range of three orders of magnitudes with the correlation coefficients ranging from 0.91 (C_24:0) to 0.99 (C_14:0). Fatty acids in sputum specimens from 21 persons were directly analyzed using the proposed method. The results show that in all the sputum specimens from patients, who were clinically diagnosed with tuberculosis (TB), tuberculosis stearic acid (TBSA) was detected, while in all the sputum samples from persons without TB, TBSA was not found. The possibility of using the proposed method to detect mycobacterium tuberculosis (MTB) via the identification of TBSA in sputum was discussed. The comparison with other methods including sputum culture and microscopy of direct smears indicated that the proposed method is fast and sensitive for the analysis of fatty acids in sputum and offers an alternative for the detection of MTB in sputum.     

Design,Synthesis, and In Vitro Anti‐mycobacterial Activities of Propylene Tethered Benzofuran–Isatin Hybrids

A series of novel propylene tethered benzofuran–isatin hybrids 5a–j were designed, synthesized, and assessed for their in vitro anti‐mycobacterial activity against Mycobacterium tuberculosis (MTB) H₃₇Rv and multidrug‐resistant (MDR)‐MTB strains. All hybrids exhibited promising anti‐mycobacterial activities against the tested two pathogens with minimum inhibitory concentration (MIC) ranging from 2 to 32 μg/mL, and the resistance index for a significant part of the hybrids was ≤1, indicating their potential for the treatment of drug‐resistant tuberculosis. Hybrid 5g (MIC: 2 and 4 μg/mL) was found to be the most active against MTB H₃₇Rv and MDR‐MTB, which was eightfold and >32‐fold more active than the first‐line anti‐tuberculosis drugs rifampicin (MIC: 32 μg/mL) and isoniazid (MIC: >128 μg/mL) against MDR‐MTB, and it could act as a starting point for further optimization.     

Design,synthesis, and in vitro antimycobacterial activities of butylene tethered 7‐fluoroisatin‐isatin scaffolds

In this work, a series of butylene tethered heteronuclear 7‐fluoroisatin‐isatin scaffolds 4a to 4h were designed and synthesized, and the antimycobacterial activity profiles, cytotoxicity together with inhibitory activity against MTB DNA gyrase, were also investigated. All the synthesized heteronuclear scaffolds were active against MTB H₃₇Rv and MDR‐MTB strains, and some of them were more potent than isoniazid ( INH ), rifampicin ( RIF ), ethambutol ( EMB ) against MDR‐MTB strain. The structure‐activity relationship demonstrated that the substituents on C‐3 position of 7‐fluoroisatin and isatin moieties were closely related with the activity, and hydrogen bond donors were favorable to the activity. Scaffolds with different substituents showed higher activity than the analogs with the same substituents at this position of the two isatin motifs, which may be attributed to the synergistic effect. Among them, the most active scaffold 4e (MIC: 1 and 4 μg/mL) was comparable with the first‐line anti‐TB agent EMB against MTB H₃₇Rv, and ≥16‐fold more potent than INH , RIF , and EMB against MDR‐MTB strain, demonstrating its potential for fighting against infections caused by both drug‐sensitive and MDR MTB strains. Moreover, scaffold 4e also possessed excellent toxicological profiles and promising inhibitory activity against MTB DNA gyrase. Thus, scaffold 4e could act as an ideal platform for further optimization.     

Chemical characterization,computational analysis and biological views on Daphne gnidioides Jaub. & Spach extracts: Can a new raw material be provided for biopharmaceutical applications?

The scientific world tends to turn to natural products such as medicinal and aromatic plants because of the inadequacy of commercially available synthetic drugs as antibiotics or anticancer, and their adverse effects on healthy tissues. One of these plants is Daphne gnidioides Jaub. & Spach, which belongs to the Thymelaeaceae family, and there is no data in the literature on its biological activity. This study is aimed to elucidate the chemical profiles and in vitro anticancer, antibacterial and DNA protection and enzyme inhibitory properties of methanol extracts of root, stem, and leaf of D. gnidioides Jaub. & Spach. Polyphenolic components of the extracts were characterized by HPLC-MS/MS. The highest phenolic content was detected in the leaf extract (TIPC = 43.5 ± 0.5 mg/g DE), followed by stem (TIPC = 27.3 ± 0.7 mg/g DE) and root (TIPC = 18.3 ± 0.2 mg/g DE) extracts. Vicenin-2 and 3-O-p-coumaroyl-5-O-caffeoylquinic acid were the main identified compounds in leaf and both root and stem extracts, respectively. The extracts did not show any protective effect on DNA against experimental Fenton’s reagent. The minimum inhibitory concentration and the minimum bactericidal concentration values for the root and leaf extracts against tested bacterial strains ranged from 31.25 to 500 μg/mL. After 48 h interaction of the cancer cell lines with the extracts, only the stem extract had significant cytotoxicity on HeLa cells (IC₅₀ = 86.16 μg/mL). No remarkable activity of the extracts, which was tested against MDA-MB-231, was detected (IC₅₀ > 1000 μg/mL). These data showed that D. gnidioides Jaub. & Spach stem extract inhibited the survival of HeLa cells in a time-dependent manner. After the treatment of IC₅₀ concentration of stem extract with HeLa cells, an increase in LC3-II autophagic gene expression was detected. Also, the extracts exhibited significant tyrosinase inhibitory effects which were confirmed by molecular docking. To sum up, the tested extracts could be used as a starting point for the development of new multifunctional drugs.     

A highly atom economic, chemo-, regio- and stereoselective synthesis, and discovery of spiro-pyrido-pyrrolizines and pyrrolidines as antimycobacterial agents

The 1,3-dipolar cycloaddition of azomethine ylides derived from acenaphthenequinone and α-amino acids viz. proline, phenylglycine and sarcosine to a series of 1-methyl-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones afforded novel spiro-pyrido-pyrrolizines and pyrrolidines chemo-, regio- and stereoselectively in quantitative yields. These compounds were screened for their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant Mycobacterium tuberculosis (MDR-TB) and Mycobacterium smegmatis using agar dilution method. Among the synthesized compounds, spiro-[2.2″]acenaphthene-1″-one-spiro[3.3′]-5′-(2-chlorophenylmethylidene)-1′-methyltetrahydro-4′(1H)-pyridinone-4-(2-chlorophenyl)hexahydro-1H-pyrrolizine (3e) was found to be the most active with a minimum inhibitory concentration (MIC) of 0.4 μg/mL against MTB and MDR-TB.