Synthesis and 3D-QSAR of p-Hydroxybenzohydrazide Derivatives With Antimicrobial Activity Against Multidrug-Resistant Staphylococcus aureus

Bhole, Ritesh P.,Bhusari, Kishore P. Korean Chemical Society 2010 대한화학회지 Vol.54 No.1

40여년전에 보고된 이래 병원에서 유래한 메치실린-저항 Staphylococcus aureus (MRSA) 은 세계적으로 큰 문제가 되어왔다. 항균성의 가능성을 가지는 새로운 약품을 개발하기 위하여 N'-[(-3-substituted-4-oxo-1,3-thiazolidin-2-ylidene]-4-hydroxy benzohydrazide (4a-4.i)와 N'-[-(3,4-disubstituted)-1,3-thiazolidin-2ylidene)]-4-hydroxybenzohydrazide (5.a-5.i)~(10.a-10.i)을 적절한 합성방법을 사용하여 합성하였다. 이들 합성된 화합물들은 s. aureus 균주에 대해 생체외 조건에서 분석하였다. 시료 화합물과 표준 화합물에 대해 최소억제농도(MIC)를 결정하였다. 시험한 모든 화합물들은 2000 ${\mu}g$/mL 투여량까지는 독성이 없었고, 사용한 균주에 대해 상당한 항균성을 보였다. 특히 6.f, 7.g, 9.f 와 10.f, 10 i 들이 가장 항균성이 컸다. 이것으로 미루어 파라-히드록시벤조히드라자이드 고리와 치환된 싸이아졸린 고리는 항균성에 필수적임을 알 수 있었다. 3D-QSAR 분석결과로 파라-히드록시벤조히드라자이드의 활성자리에 대한 결합방식을 알게되었다. Hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) has been an increasing problem worldwide since the initial reports over 40 years ago. To examine new drug leads with potential antibacterial activities, Various N'-[(-3-substituted-4-oxo-1,3-thiazolidin-2-ylidene]-4-hydroxy benzohydrazide (4a-4.i) and N'-[-(3,4-disubstituted)-1,3-thiazolidin-2ylidene)]-4-hydroxybenzohydrazide from (5.a-5.i) to (10.a-10.i) were synthesized using appropriate synthetic route. The entire test compounds (4.a-4.i) and from (5.a-5.i) to (10.a-10.i) were assayed in vitro against s. aureus strain. The minimum inhibitory concentration (MIC) was determined for test compounds and for reference standards. The test compounds showed significant antibacterial activity against the strains used, when tested in vitro. In general, p-hydroxybenzohydrazide ring and substituted thiazoline ring are essential for antimicrobial activity. Among the compounds tested, compounds 6.f, 7.g, 9.f and 10.f, 10 i were found to be most potent. The test compounds were found nontoxic upto the dose level of 2000 ${\mu}g$/mL. The intact compounds were then subjected for 3D-QSAR studies. 3D-QSAR study based on the principal of alignment of pharmacophoric features by Schrodinger PHASE module. The 3D-QSAR study allowed us to confirm the preferential binding mode of p-hydroxybenzohydrazide inside the active site.

Design and Synthesis of p-hydroxybenzohydrazide Derivatives for their Antimycobacterial Activity

Bhole, Ritesh.P.,Borkar, Deepak.D.,Bhusari, Kishore.P.,Patil, Prashant.A. Korean Chemical Society 2012 대한화학회지 Vol.56 No.2

The main mycobacterial infection in human is tuberculosis caused by Mycobacterium tuberculosis. Tuberculosis is the leading infectious cause of death in the world. Therefore there is continuing and compelling need for new and improved treatment for tuberculosis. The entire logic towards design of new compounds containing 4-hydroxy-N'-(1,3-thiazoldin- 2-yldene)benzohydrazide moiety is basically for superior antimycobacterial activity. The recent advances in QSAR and computer science have provided a systematic approach to design a structure of any compound and further, the biological activity of the compound can be predicted before synthesis. The 3D-QSAR studies for the set of 4-hydroxy-N'-(1,3-thiazoldin- 2-yldene)benzohydrazide and their derivatives were carried out by using V-life MDS (3.50). The various statistical methods such as Multiple Linear Regression (MLR), Partial Least Square Regression (PLSR), Principle Component Regression(PCR) and K nearest neighbour (kNN) were used. The kNN showed good results having cross validated $r^2$ 0.9319, $r^2$ for external test set 0.8561 and standard error of estimate 0.2195. The docking studies were carried out by using Schrodinger GLIDE module which resulted in good docking score in comparison with the standard isoniazid. The designed compounds were further subjected for synthesis and biological evaluation. Antitubercular evaluation of these compounds showed that (4.a), (4.d) and (4.g) found as potent inhibitor of H37RV.

OPTIMIZATION OF DIETS WITH EQUAL QUANTITY OF PROTEIN DERIVED FROM FOOD LEGUME AND CEREAL FOR HARD WORKING RURAL POOR USING LINEAR PROGRAMMING APPROACH

S . D . Kulkarni,N . G . Bhole,S . K . Sawarkar 한국농업기계학회 1993 ICAMPE 요약집 Vol.2 No.-

Structural, Optical and Thermo Electrical Properties of Nanostructured Vacuum Evaporated CdS Thin Films

M.S. Kale,Y.R. Toda,M.P. Bhole,D. S. Bhavsar 대한금속·재료학회 2014 ELECTRONIC MATERIALS LETTERS Vol.10 No.1

Nano structured thin films having different thickness of CdS were deposited by thermal evaporation techniques, onto precleaned amorphous glass substrate at room temperature. The structural properties of films were evaluated by XRD, Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM). The quantitative analysis was done by Energy Dispersive Analysis for x-ray to determine atomic % of the material used. The optical band gaps of the films were measured by using optical absorption spectra. Thermo Electrical parameters such as Fermi energy (0.098 to 0.006 eV), absorption coefficient (1.04 to 1.16) have been estimated. The x-ray diffraction analysis confirms that films are polycrystalline in nature having orthorhombic structure with a preferential orientation along the (040) plane. The degree of such a preferred orientation was found to increase with film thickness. The lattice parameters (a = 14.315, b = 14.568 and c = 14.074 Å) and crystallite size (D) were calculated and found to be 242.9 nm. Unit cell volume is found to be 2935. SEM investigation confirms that films were uniformly deposited over the surface and particles were granular in nature. The particle size was determined by using SEM and found to be 6.88 -10.8 6 nm. It is found that CdS is direct band gap material having value of 2.42 eV.

Is long term storage of cryopreserved stem cells for hematopoieticstem cell transplantation a worthwhile exercise in developingcountries?

Santhosh Kumar Devadas,Minal Khairnar,Sumathi S Hiregoudar,Shashank Ojha,Sachin Punatar,Alok gupta,Anant Gokarn,Pallavi Bhole,Sadhana Kannan,Navin Khattry 대한혈액학회 2017 Blood Research Vol.51 No.4

Background: Stem cell units (SCUs) that are cryopreserved prior to both autologous and allogeneic hematopoietic stem cell transplants (for donor lymphocyte infusion) remain unused or partially used several times, and become an increased burden to blood banks/SCU repositories. Because of the scarcity of data regarding the duration for which the storage is useful, there is no general consensus regarding disposal of SCUs. Methods: We conducted a retrospective audit of SCU utilization in 435 patients who planned to undergo either autologous stem cell transplantation (auto-SCT) (N=239) or allogeneic stem cell transplantation (allo-SCT) (N=196) at a tertiary cancer care center between November 2007 to January 2015. Results: Our cohort consisted of 1,728 SCUs stored for conducting auto-SCT and 729 SCUs stored for conducting donor lymphocyte infusions (DLIs) after allo-SCT. Stem cells were not in-fused in 12.5% of patients who had planned to undergo auto-SCT, and 80% of patients who underwent allo-SCT never received DLI. Forty-one percent of SCUs intended for use in auto-SCT remained unutilized, with a second auto-SCT being performed only in 4 patients. Ninety-four percent of SCUs intended for carrying out DLIs remained unused, with only minimal usage observed one year after undergoing allo-SCT. Conclusion: The duration of storage of unused SCUs needs to be debated upon, so that a consensus can be reached regarding the ethical disposal of SCU.

Is long term storage of cryopreserved stem cells for hematopoieticstem cell transplantation a worthwhile exercise in developingcountries?

Santhosh Kumar Devadas,Minal Khairnar,Sumathi S Hiregoudar,Shashank Ojha,Sachin Punatar,Alok gupta,Anant Gokarn,Pallavi Bhole,Sadhana Kannan,Navin Khattry 대한혈액학회 2017 Blood Research Vol.52 No.4

Background: Stem cell units (SCUs) that are cryopreserved prior to both autologous and allogeneic hematopoietic stem cell transplants (for donor lymphocyte infusion) remain unused or partially used several times, and become an increased burden to blood banks/SCU repositories. Because of the scarcity of data regarding the duration for which the storage is useful, there is no general consensus regarding disposal of SCUs. Methods: We conducted a retrospective audit of SCU utilization in 435 patients who planned to undergo either autologous stem cell transplantation (auto-SCT) (N=239) or allogeneic stem cell transplantation (allo-SCT) (N=196) at a tertiary cancer care center between November 2007 to January 2015. Results: Our cohort consisted of 1,728 SCUs stored for conducting auto-SCT and 729 SCUs stored for conducting donor lymphocyte infusions (DLIs) after allo-SCT. Stem cells were not in-fused in 12.5% of patients who had planned to undergo auto-SCT, and 80% of patients who underwent allo-SCT never received DLI. Forty-one percent of SCUs intended for use in auto-SCT remained unutilized, with a second auto-SCT being performed only in 4 patients. Ninety-four percent of SCUs intended for carrying out DLIs remained unused, with only minimal usage observed one year after undergoing allo-SCT. Conclusion: The duration of storage of unused SCUs needs to be debated upon, so that a consensus can be reached regarding the ethical disposal of SCU.

Immunohistochemical Profile of Breast Cancer Patients at a Tertiary Care Hospital in New Delhi, India

Doval, Dinesh Chandra,Sharma, Anila,Sinha, Rupal,Kumar, Kapil,Dewan, Ajay Kumar,Chaturvedi, Harit,Batra, Ullas,Talwar, Vineet,Gupta, Sunil Kumar,Singh, Shailendra,Bhole, Vidula,Mehta, Anurag Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.12

Background: To assess the immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor-2 (HER2) neu receptor in breast cancer and their associations with various clinicopathological characteristics. Materials and Methods: This is a retrospective analysis of women who presented with primary, unilateral breast cancer in the Department of Medical Oncology at Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India during the period from January 2008 to December 2011. Data were retrieved from the medical records of the hospital including both early and locally advanced cancer cases. ER, PgR and HER2neu expression in these patients was assessed and triple negative patients were identified. Associations of triple negative and non-triple negative groups with clinicopathological characteristics were also evaluated. Results: A total of 1,284 women (mean age 52.1 years, 41.9% premenopausal) were included in the analysis. Hormone receptor positivity (ER and/or PgR) was seen in 63.4% patients, while 23.8% of tumors were triple negative. Only 23.0% were HER2 positive. Around 10.0% of tumors were both ER and HER2 positive. ER and PgR positivity was significantly associated with negative HER2 status (p-value <0.0001). Younger age, premenopausal status, higher tumor grade, lymph node negativity, advanced cancer stage, and type of tumor were strongly associated with triple negativity. Significantly, a smaller proportion of women had ductal carcinoma in situ in the triple negative group compared with the non-triple negative group (35.6% versus 60.8%, p-value<0.01). Conclusions: The present analysis is one of the largest studies from India. The majority of the Indian breast cancer patients seen in our hospital present with ER and PgR positive tumors. The triple negative patients tended to be younger, premenopausal, and were associated with higher tumor grades, negative lymph nodes status and lower frequency of ductal carcinoma in situ.